Assisted reproductive technology (ART) encompasses all medical interventions that involve the handling of human eggs, sperm, or embryos outside the body to facilitate pregnancy, primarily addressing infertility through procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and gamete intrafallopian transfer (GIFT).[1][2]
The field's breakthrough occurred in 1978 with the birth of Louise Brown, the first infant conceived via IVF, developed by Robert Edwards, Patrick Steptoe, and Jean Purdy after decades of animal research and ethical debates.[3][4]
By 2023, ART contributed to over 95,000 births in the United States alone, representing about 2% of total births, with success rates for live births per IVF cycle averaging around 55% for women under 35 but dropping sharply to under 5% for those over 43, influenced by factors like embryo quality and maternal age.[5][6]
Key achievements include preimplantation genetic testing to reduce chromosomal abnormalities and cryopreservation techniques enabling deferred reproduction, yet these are tempered by higher risks of multiple pregnancies, preterm birth, and low birth weight compared to natural conception.[7][8]
Controversies persist over the destruction of surplus embryos, the ethics of gamete donation and surrogacy, unequal access due to high costs often exceeding $15,000 per cycle without insurance coverage, and potential long-term health effects on ART-conceived children, including elevated incidences of imprinting disorders and cardiovascular issues, underscoring ongoing debates about the commodification of human reproduction and its deviation from natural procreative processes.[9][7]
Definition and overview
Core definition and scope
Assisted reproductive technology (ART) encompasses medical procedures and treatments that involve the laboratory handling of human oocytes, sperm, or embryos to facilitate pregnancy in individuals or couples facing infertility or other reproductive challenges.[10] According to the Centers for Disease Control and Prevention, ART specifically includes all fertility treatments where eggs or embryos are handled outside the body, such as through surgical retrieval, fertilization in vitro, or embryo culture and transfer.[2] This definition, established in U.S. federal law under 42 U.S.C. § 263a-7, emphasizes the in vitro manipulation as the distinguishing criterion, excluding simpler interventions like timed intercourse or basic ovulation induction without gamete handling.[10]The scope of ART is primarily focused on overcoming barriers to natural conception, including tubal factor infertility, severe male factor infertility, advanced maternal age, or genetic conditions necessitating preimplantation testing.[11] Core procedures within this scope, such as in vitro fertilization (IVF)—which accounted for over 99% of ART cycles reported to the CDC in recent years—entail controlled ovarian hyperstimulation, oocyte retrieval, fertilization, embryo development, and transfer to the uterus.[2][12] While adjunctive techniques like cryopreservation extend ART's utility, the field's boundaries are drawn at interventions requiring ex vivo handling, differentiating it from non-laboratory fertility aids.[13]ART's application extends beyond heterosexual couples to include same-sex couples, single individuals, and gestational surrogacy arrangements, provided the procedural criteria are met, reflecting its role in addressing diverse reproductive needs rather than solely biological infertility.[14] Empirical data from surveillance systems indicate that ART contributes to approximately 2% of U.S. births annually, underscoring its targeted yet impactful scope in modern reproductive medicine.[15]
Key components and processes
Assisted reproductive technology (ART) involves a series of coordinated medical and laboratory processes designed to overcome infertility by manipulating gametes and embryos ex vivo. Central to ART is the handling of humanoocytes, sperm, or embryos to achieve fertilization and implantation, distinguishing it from less invasive methods like intrauterine insemination.[1] The core processes typically commence with controlled ovarian hyperstimulation to recruit multiple follicles, followed by oocyte retrieval, gamete preparation, fertilization, embryo culture, and culminating in embryo transfer to the uterus.[11]Ovarian stimulation represents a foundational component, employing exogenous gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) analogs administered via subcutaneous injections for 8 to 14 days to promote multifollicular development in the ovaries.[16] This phase is closely monitored through serial transvaginal ultrasounds and serum estradiol measurements to assess follicular growth and prevent complications like ovarian hyperstimulation syndrome.[17] Upon reaching maturity—typically when leading follicles measure 18-20 mm—a trigger injection of human chorionic gonadotropin (hCG) or a GnRH agonist induces final oocyte maturation, occurring approximately 36 hours prior to retrieval.[11]Oocyte retrieval, a minimally invasive surgical procedure, involves transvaginal ultrasound-guided aspiration of mature follicles under light sedation or anesthesia, yielding an average of 10-15 eggs per cycle in successful stimulations.[16] Concurrently, semen is collected and processed to isolate motile sperm via techniques such as density gradient centrifugation or swim-up methods, ensuring optimal fertilization conditions.[11] Fertilization occurs in the laboratory either through conventional insemination, where 50,000-100,000 motile sperm are co-incubated with each oocyte, or intracytoplasmic sperm injection (ICSI) for cases of male factor infertility, involving direct sperm injection into the oocytecytoplasm.[17]Post-fertilization, embryos are cultured in specialized incubators mimicking physiological conditions, with development monitored to the cleavage stage (day 3) or blastocyst stage (day 5-6), allowing selection of viable embryos based on morphology and, optionally, genetic integrity.[11]Embryo transfer then entails depositing one or more selected embryos into the uterine cavity via a thin catheter under ultrasound guidance, typically without anesthesia, followed by luteal phase support with progesterone to sustain endometrial receptivity.[16] Surplus embryos may undergo cryopreservation using vitrification techniques for future use, preserving viability rates comparable to fresh transfers.[17] These processes, while standardized, are tailored to individual patient factors such as age and diagnosis to optimize outcomes.[11]
Distinctions from natural reproduction
Assisted reproductive technology (ART) fundamentally differs from natural reproduction in the site and mechanism of fertilization. In natural conception, spermatozoa are deposited in the female reproductive tract via intercourse, migrate to the fallopian tube, and fertilize the oocytein vivo within a complex physiological environment involving natural selection pressures and maternal-embryonic interactions.[18] By contrast, ART procedures such as in vitro fertilization (IVF) involve ovarian stimulation with gonadotropins, surgical oocyte retrieval via transvaginal aspiration, extracorporeal fertilization in a controlled laboratory medium, and subsequent embryo culture before uterine transfer, bypassing natural gamete transport and initial embryonic development stages.[15] This ex vivo process introduces artificial conditions, including synthetic culture media and incubators mimicking but not replicating tubal milieu, potentially altering early embryonic gene expression and epigenetic programming.[19]ART enables unprecedented intervention in gamete and embryo selection, absent in natural reproduction. Techniques like intracytoplasmic sperm injection (ICSI) directly inject a single spermatozoon into the oocyte, circumventing natural barriers such as zona pellucida penetration and acrosome reaction, which may select for sperm motility and viability.[20] Preimplantation genetic testing allows screening for aneuploidy or monogenic disorders, permitting selection of embryos with desired genetic profiles, whereas natural reproduction relies on stochastic fertilization without such diagnostic or selective capabilities.[21]Cryopreservation of gametes or embryos further decouples reproduction from immediate post-ovulatory timing, enabling deferred transfers that can synchronize with optimal endometrial receptivity but expose embryos to vitrification and thawing stresses not encountered naturally.[22]Health outcomes diverge significantly, with ART-associated pregnancies exhibiting elevated perinatal risks compared to spontaneous conceptions, even after adjusting for confounders like maternal age and parity. Singleton ART births show increased incidences of preterm delivery (relative risk approximately 1.5–2.0), low birth weight, and congenital malformations (odds ratio 1.22, 95% CI 1.17–1.27), attributable in part to underlying infertility, ovarian hyperstimulation, and embryonic manipulation rather than solely procedural artifacts.[23][24] Multiple gestations, historically more common in ART due to multi-embryo transfers (now mitigated by single-embryo policies), amplify risks of preeclampsia, gestational diabetes, and neonatal intensive care admission, exceeding rates in naturally conceived multiples.[25] Longitudinally, ART-conceived offspring display subtle epigenetic alterations, such as genome-wide hypomethylation, and potential elevations in cardiovascular or neurodevelopmental vulnerabilities, though causality remains debated amid confounding by parental subfertility.[19][26] Maternal morbidity, including ovarian hyperstimulation syndrome (affecting 1–5% of stimulated cycles) and higher cesarean rates (often >50% in ART), contrasts with the lower procedural invasiveness of natural reproduction.[27]
Historical development
Early historical attempts and concepts
The discovery of spermatozoa in 1677 by Antonie van Leeuwenhoek, using early microscopes to observe humansemen samples, provided the first empirical insight into the cellular basis of fertilization, challenging pre-existing theories like preformationism and enabling conceptual frameworks for artificial intervention in reproduction.[28] This observation, confirmed independently by Christiaan Huygens, shifted understandings from vague humoral models to a particulate view of seminal contribution, though debates persisted on whether sperm or eggs contained preformed organisms.[28]In the late 18th century, Lazzaro Spallanzani advanced experimental approaches by achieving the first documented successful artificial insemination in a viviparous mammal, inseminating a female dog with collected semen in 1784, which resulted in a litter of three puppies after 62 days of gestation.[28] Spallanzani's work, building on frog fertilization experiments, demonstrated that semen could be artificially introduced to bypass natural copulation while maintaining viability, though he erroneously concluded that semen required contact with the male body for activation.[29] These animal trials, rooted in Enlightenmentempiricism, established proof-of-principle for assisted fertilization but highlighted challenges like semen motility loss outside the body.Human applications emerged tentatively around 1790, when Scottish surgeon John Hunter reportedly performed the first artificial insemination using a warmed syringe to deposit a linen draper's semen directly into his wife's vagina, addressing the husband's hypospadias; the procedure allegedly led to pregnancy and a healthy child.[28] Though often cited as the inaugural human case, documentation remains anecdotal and contested, with later analyses questioning its verification.[30] By the mid-19th century, donor insemination appeared, as in the 1884 case by J. Marion Sims and William Pancoast, who secretly used a medical student's semen to impregnate an infertile patient's wife without disclosure, yielding a child but raising early ethical concerns over consent and deception.[31] These rudimentary efforts, confined to intracervical or intrauterine deposition, underscored causal necessities like timely semen delivery but were limited by incomplete knowledge of ovulation timing and lacked systematic success metrics.
Mid-20th century foundations
The foundations of assisted reproductive technology in the mid-20th century were established through advancements in artificial insemination and hormone therapies, addressing primary causes of infertility such as male factor issues and anovulation. In 1943, Alan Guttmacher documented the first systematic use of human artificial insemination (AI), primarily donor insemination to bypass male infertility, marking a pivotal shift toward clinical application of reproductive assistance.[32] By the 1940s, synthetic hormone analogs emerged, enabling targeted stimulation of reproductive processes and laying groundwork for controlled ovulation.[32]A major breakthrough occurred in 1953 when Jerome K. Sherman successfully cryopreserved human sperm using glycerol as a cryoprotectant, retaining its fertilizing capacity after thawing; this led to the first reported human pregnancy and live birth from frozen-thawed sperm, facilitating sperm banking and posthumous or delayed reproduction.[32][33][34] These techniques expanded AI's viability, with survival rates reaching 67% in early trials, and supported broader access to fertility preservation amid rising demand for infertility treatments.[35]Ovulation induction advanced in the late 1950s with Carl Gemzell's 1958 report of successful superovulation using human pituitary-derived gonadotropins extracted from postmenopausal urine, inducing follicle development and pregnancy in anovulatory women.[36] This built on earlier animal studies, including Min Chueh Chang's 1959 achievement of the first live birth from in vitro fertilization in rabbits, demonstrating mammalian oocyte fertilization outside the body and informing human protocols.[37] By the 1960s, human menopausal gonadotropin (hMG) preparations refined these methods, yielding the first pregnancies from stimulated cycles and setting the stage for embryo transfer integration.[38] These empirical strides emphasized causal interventions in gamete viability and hormonal regulation, prioritizing data-driven refinements over speculative approaches.
IVF era and major milestones since 1978
The in vitro fertilization (IVF) era commenced with the birth of Louise Brown on July 25, 1978, at Oldham and District General Hospital in England, marking the first successful live birth from human IVF.30261-9/fulltext) This achievement resulted from the collaboration between gynecologist Patrick Steptoe and physiologist Robert Edwards, who had been refining IVF techniques since the 1960s, including laparoscopic egg retrieval and embryo culture.[39] Edwards received the Nobel Prize in Physiology or Medicine in 2010 for this work, recognizing the foundational role of IVF in treating infertility despite initial ethical controversies.[40]In the early 1980s, IVF rapidly expanded internationally, with the first U.S. IVF birth occurring on December 28, 1981, when Elizabeth Carr was delivered in Norfolk, Virginia.[41] A key advancement was embryo cryopreservation, enabling storage and later transfer of embryos; the first live birth from a cryopreserved humanembryo took place in 1984 in Australia, following a pregnancy reported in 1983.[42] This technique improved efficiency by allowing multiple embryo transfers from a single stimulation cycle and became integral to IVF protocols, with vitrification later enhancing survival rates.[43] By the mid-1980s, IVF success rates were low—around 5-10% per cycle—but procedural refinements, such as controlled ovarian hyperstimulation, increased oocyte yields and implantation potential.[40]The 1990s introduced transformative techniques addressing specific infertility causes. Intracytoplasmic sperm injection (ICSI), pioneered in 1992 by Gianpiero Palermo and colleagues in Belgium, involved direct injection of a single spermatozoon into an oocyte, revolutionizing treatment for severe male factor infertility where conventional IVF fertilization rates were near zero.[44] The first ICSI live births were reported in 1992, and by the early 2000s, ICSI accounted for over 70% of IVF cycles globally due to its efficacy in bypassing natural barriers to fertilization.[45] Concurrently, preimplantation genetic diagnosis (PGD), first successfully applied in 1990 for sex-linked disorders by selecting female embryos, enabled early detection of genetic abnormalities via biopsy of polar bodies or blastomeres.[46] This evolved into preimplantation genetic testing (PGT), incorporating comprehensive chromosomal screening to reduce miscarriage rates and aneuploidy-related failures.[47]Subsequent decades focused on optimization and adjuncts. In the 2000s, blastocyst culture—extending embryo growth to day 5—improved selection of viable embryos, correlating with higher implantation rates per transfer.[40] Time-lapse imaging emerged in the 2010s, providing non-invasive morphokinetic assessments to predict embryo viability without disrupting culture conditions.[48] Recent advancements in the 2020s include artificial intelligence algorithms for embryo selection, trained on vast datasets to forecast ploidy and developmental potential, potentially boosting live birth rates beyond traditional morphology-based methods.[49] Automated systems for micromanipulation and culture have also enhanced procedural consistency, though long-term data on offspring health remains essential for validation.[50] Overall, cumulative live birth rates per IVF cycle have risen from under 10% in the 1980s to 40-50% for women under 35 by the 2020s, driven by these iterative improvements.[51]
Technical procedures
Fundamental steps in ART cycles
Assisted reproductive technology (ART) cycles, most commonly exemplified by in vitro fertilization (IVF), consist of a series of coordinated medical and laboratory procedures designed to facilitate conception outside the body. These cycles typically begin with hormonal preparations and span 4 to 6 weeks, encompassing ovarian stimulation to generate multiple oocytes, their surgical retrieval, laboratory fertilization, embryo development, and uterine transfer.[11] The process aims to overcome barriers to natural fertilization by controlling key reproductive variables, with success dependent on patient-specific factors like age and ovarian reserve.[14]The initial phase involves controlled ovarian stimulation (COS), where exogenous gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) analogs are administered daily via subcutaneous injections for 8 to 14 days to recruit and grow multiple ovarian follicles, targeting 10 to 20 mature oocytes per cycle.[8] This step, used in the vast majority of IVF cycles, contrasts with natural cycles by amplifying egg production to increase embryo availability and mitigate the impact of potential oocyte aneuploidy.[8] Concurrent monitoring through transvaginal ultrasound and serum estradiol measurements adjusts dosing to prevent ovarian hyperstimulation syndrome (OHSS), a potential complication involving excessive follicular response.[11]Upon achieving adequate follicular maturity (typically follicles ≥18 mm in diameter), ovulation triggering occurs with human chorionic gonadotropin (hCG) or a gonadotropin-releasing hormone (GnRH) agonist injection, administered 34 to 36 hours prior to oocyte retrieval to induce final meiotic resumption without premature luteinizing hormone surges.[8] This timing optimizes oocyte maturity while minimizing post-maturation aging effects on fertilization potential.[11]Oocyte retrieval, or follicular aspiration, follows as a transvaginal ultrasound-guided procedure under mild sedation, where a needle punctures mature follicles to aspirate follicular fluid containing oocytes, yielding an average of 10 to 15 eggs per cycle in stimulated patients.[14] Retrieved oocytes are immediately transferred to a controlled laboratory environment for assessment and preparation.[11]Simultaneously, sperm collection and preparation involves semen analysis and processing via density gradient centrifugation or swim-up techniques to select motile spermatozoa, with intracytoplasmic sperm injection (ICSI) employed for male factor infertility by directly injecting a single spermatozoon into the oocytecytoplasm.[11] Fertilization occurs in vitro by co-incubating oocytes with prepared sperm or via ICSI, with success confirmed 16 to 18 hours later by the presence of two pronuclei indicating zygote formation.[8]Subsequently, embryo culture maintains fertilized oocytes in specialized media under precise temperature, pH, and gas conditions for 3 to 5 days, progressing from cleavage-stage embryos to blastocysts for improved implantation potential and euploidy selection.[11] Embryos may undergo preimplantation genetic testing (PGT) for aneuploidy to enhance transfer outcomes.[8]The cycle culminates in embryo transfer, a minimally invasive catheter-based procedure depositing 1 to 2 selected embryos into the uterine cavity, typically at the blastocyst stage on day 5 post-retrieval, without anesthesia.[11]Luteal phase support with progesterone supplementation follows to sustain endometrial receptivity until pregnancy confirmation via serum hCG testing 9 to 14 days after transfer.[8] Excess embryos may be cryopreserved for future cycles.[14]
Primary techniques including IVF and ICSI
In vitro fertilization (IVF) represents the foundational technique in assisted reproductive technology, wherein oocytes are retrieved from the ovaries, fertilized with spermatozoa in a laboratory setting, and resulting embryos are cultured before transfer to the uterus. The procedure commences with controlled ovarian hyperstimulation, typically involving administration of gonadotropins such as follicle-stimulating hormone (FSH) for 8-14 days to promote multifollicular development, monitored via transvaginal ultrasound and serum estradiol levels.[8] Ovulation is triggered by human chorionic gonadotropin (hCG) injection approximately 36 hours prior to oocyte retrieval, which is performed under ultrasound guidance using a needle to aspirate follicular fluid containing mature oocytes.[14] Retrieved oocytes, averaging 10-15 per cycle in successful stimulations, undergo conventional insemination with prepared spermatozoa or intracytoplasmic sperm injection, followed by embryo culture for 3-5 days to the cleavage or blastocyst stage.[8] Selected embryos, often 1-2 to minimize multiple gestation risks, are transferred transcervically into the endometrial cavity.[52]Intracytoplasmic sperm injection (ICSI) serves as a specialized fertilization method integrated into IVF cycles, particularly for severe male factor infertility characterized by low sperm count, motility, or morphology. In ICSI, a single motile spermatozoon is selected and microinjected directly into the ooplasm of a metaphase II oocyte using a fine glass micropipette under an inverted microscope with micromanipulators, bypassing natural barriers such as the zona pellucida and oolemma.[53] Sperm preparation involves density gradient centrifugation to isolate viable cells, and the injection occurs shortly after oocyte denudation from cumulus cells. This technique achieves fertilization rates of 70-80% with ejaculated spermatozoa, comparable to or exceeding conventional IVF in non-male factor cases, though it is routinely applied even absent male infertility to maximize outcomes in low-oocyte-yield cycles.[54][55] Post-injection, injected oocytes are cultured similarly to standard IVF embryos, with fertilization confirmed by pronuclear visualization 16-18 hours later.[56]While conventional IVF relies on sperm-oocyte co-incubation allowing capacitation and acrosome reaction, ICSI circumvents these processes, enabling fertilization with immotile or surgically retrieved sperm, as in cases of obstructive azoospermia. Introduced in 1992, ICSI has become ubiquitous in ART, comprising over 90% of fertilization attempts in many clinics due to its efficacy and to mitigate unpredictable fertilization failure.[57] Both techniques necessitate embryo quality assessment via morphology or adjunctive genetic screening prior to transfer, with surplus embryos eligible for cryopreservation.[8]
Preimplantation genetic testing (PGT) enables the screening of embryos for genetic abnormalities prior to transfer in assisted reproductive technology cycles. It encompasses PGT for aneuploidy (PGT-A), which assesses whole-chromosome abnormalities; PGT for monogenic/single-gene defects (PGT-M), targeting specific inherited disorders like cystic fibrosis; and PGT for structural rearrangements (PGT-SR), identifying balanced or unbalanced chromosomal translocations.[58] The procedure typically involves trophectoderm biopsy of blastocyst-stage embryos on day 5 or 6 post-fertilization, followed by genetic analysis using next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), or quantitative PCR, with embryos then cryopreserved pending results.[59] First applied successfully in 1989 for sex-linked disorders, PGT has evolved with trophectoderm biopsy preferred over earlier polar body or cleavage-stage methods due to higher accuracy (98-100% for meiotic errors) and lower risk of embryo harm.[58]While PGT-A aims to select euploid embryos to improve implantation and reduce miscarriage rates, randomized controlled trials (RCTs) and meta-analyses indicate no consistent benefit in cumulative live birth rates (LBR) compared to unscreened transfers. For instance, the STAR trial (2019) reported ongoing pregnancy rates of 50% versus 46% per transfer, and a 2021 China RCT showed LBR of 77.2% versus 81.8% overall.[59] Potential advantages may exist for women over 37 years, those with recurrent pregnancyloss, or repeated implantation failure, where post-hoc analyses suggest higher per-transfer LBR, though evidence remains limited and not universally supportive of routine use.[59] Risks include biopsy-induced embryo damage, misdiagnosis from mosaicism (present in up to 20-30% of blastocysts), and discarding potentially viable embryos, with no significant differences in neonatal outcomes observed but ethical concerns over embryo selection persisting.[58] PGT-M and PGT-SR offer higher diagnostic precision for known risks but require custom test development and carry limitations from genetic heterogeneity.[58]Cryopreservation complements ART by preserving gametes, zygotes, or embryos for deferred use, with vitrification—the rapid cooling method using high cryoprotectant concentrations—supplanting slow-freezing since the early 2000s due to superior post-thaw viability.[60]Embryo survival rates exceed 90% after vitrification, oocyte survival reaches 85-90% (age-dependent, with >20% loss in women over 35), and sperm cryopreservation yields high post-thaw motility with comparable fertilization and pregnancy outcomes to fresh samples in IVF cycles.[60]Frozenembryo transfers (FET) achieve live birth rates equivalent to or higher than fresh transfers in high responders or polycystic ovary syndrome patients, often integrated with PGT-A for single euploid transfers, though cumulative LBR per cycle may not differ significantly in normo-responders.[60]Elective cryopreservation supports fertility preservation, with cryopreserving ≥20 mature oocytes before age 38 conferring a 70% chance of live birth via IVF.[61] Risks include obstetric complications like elevated preeclampsia (up to 50% higher in FET versus fresh) and large-for-gestational-age infants, potentially linked to endometrial preparation or freeze-thaw processes, alongside investigational concerns over epigenetic alterations, though long-term offspring health data show no major deviations.[60] Sperm cryopreservation poses minimal added risk, routinely used in male factor infertility with fertilization rates of 84-87% post-thaw.[60] Overall, these adjunctive methods enhance ART flexibility but require patient-specific application given variable efficacy and procedural costs.[59]
Efficacy and outcomes
Success rates and metrics
Live birth rates, defined as the number of deliveries resulting in at least one live-born infant (gestational age ≥20 weeks or birth weight ≥400g), serve as the primary metric for assessing assisted reproductive technology (ART) efficacy, as they account for pregnancy losses unlike clinical pregnancy rates, which detect a gestational sac via ultrasound but incur a ~19% attrition to live birth.[62][62] Success is reported per initiated cycle (including all steps from stimulation to potential transfer), per oocyte retrieval, per embryo transfer, or cumulatively across multiple cycles using the same cohort of oocytes/embryos.[63] Per-transfer rates exceed per-cycle rates due to cancellations (e.g., poor response or no viable embryos), while frozen embryo transfers (FET) often yield higher outcomes than fresh transfers owing to optimized endometrial conditions post-stimulation.[64] Cumulative live birth rates (CLBR) over 2-3 cycles typically double single-cycle figures, reaching 50-70% for women under 35 with good prognosis, though they plateau with diminishing returns in low-responder groups.[65][66]In the United States, national ART data from 2023 reflect over 390,000 IVF cycles yielding ~95,000 live births, with overall live birth rates per intended retrieval around 30-40% for autologous cycles, varying by protocol and patient factors.[67][5] Maternal age profoundly influences outcomes: for autologous oocytes, live birth rates per embryo transfer are ~48% for women under 35, declining to ~41% at 35-37, ~30% at 38-40, ~15-20% at 41-42, and <5-10% over 43, reflecting oocyte quantity and aneuploidy increases.[68][69] Donor oocyte cycles achieve 42-52% live birth rates per transfer across ages, underscoring gamete quality's dominance.[70]European data from registries align closely, with 2023 UK figures showing ~33% live birth per FET embryo transfer and ~26-32% per fresh IVF/ICSI cycle, stagnant over decades despite procedural advances due to rising treatment of older patients and complex cases.[71][66]
Maternal Age (Autologous Oocytes, US Data)
Live Birth Rate per Embryo Transfer (%)
Live Birth Rate per Cycle Started (%)
<35
45-50
30-35
35-37
35-40
25-30
38-40
20-25
15-20
41-42
10-15
5-10
>42
<10
<5
These rates derive from national aggregates like CDC/SART summaries, which provide less selection bias than clinic-specific reports; actual patient outcomes may vary with infertility etiology (e.g., higher for tubal factors, lower for diminished ovarian reserve) and adjuncts like preimplantation genetic testing, which boost per-transfer efficiency but not always CLBR in good-prognosis groups.[6][72][73]
Factors affecting efficacy
Maternal age is the most significant predictor of success in assisted reproductive technology (ART), with live birth rates per cycle declining sharply after age 35 due to reduced oocyte quantity and quality. For women under 35 years, live birth rates from autologous oocytes average around 45-50% per cycle, dropping to 30-35% for ages 35-37, 20-25% for 38-40, and below 10% for those over 42, based on U.S. national data from over 400,000 ART cycles.[6] This age-related decline reflects diminished ovarian reserve and increased chromosomal abnormalities in eggs, independent of other interventions.[74]Ovarian reserve markers, such as anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH), strongly correlate with the number of oocytes retrieved and subsequent pregnancy rates. Higher AMH (>1.5 ng/mL) and AFC (>10) predict better response to ovarian stimulation, yielding more embryos and higher live birth probabilities, while low reserve (e.g., AMH <0.5 ng/mL) halves success odds even in younger patients.[74] The underlying infertility diagnosis also modulates efficacy; tubal factor infertility yields higher rates (up to 40% live births) compared to diminished ovarian reserve or endometriosis (20-30%), as the former allows use of unaffected gametes.[75]Embryo quality, assessed via morphology grading or preimplantation genetic testing (PGT), profoundly influences implantation and live birth rates, with top-grade blastocysts (e.g., 4AA) achieving 50-60% success per transfer versus 20-30% for poorer grades.[76] Transferring multiple embryos increases cumulative live birth rates modestly (e.g., from 40% with single embryo transfer to 50% with two) but elevates multiple gestation risks without proportional efficacy gains in euploid transfers.[77] Sperm parameters, including motility and DNA fragmentation, impact intracytoplasmic sperm injection (ICSI) outcomes, reducing fertilization rates by 10-20% in severe male factor cases.[74]Lifestyle factors independently affect ART efficacy; obesity (BMI >30 kg/m²) lowers live birth odds by 20-50% through impaired oocyte maturation, reduced endometrial receptivity, and suboptimal stimulation response, with systematic reviews confirming dose-dependent negative effects.[78]Smoking decreases clinical pregnancy rates by 15-20% and live births by 10-15% via oocyte toxicity and vascular damage, with meta-analyses showing consistent detriment even at low exposure levels.[79] Other modifiable elements, like alcohol intake and caffeine excess, show weaker but adverse associations in cohort studies.[80]Cycle-specific variables, including stimulation protocol intensity and prior ART attempts, further modulate outcomes; cumulative live birth rates reach 60-70% after three cycles in good-prognosis patients, but dropout and endometrial factors (e.g., thin lining <7 mm) reduce per-cycle efficacy by 30%.[81] Clinic-level differences in laboratory conditions and operator experience contribute up to 10-15% variance in success, underscoring procedural quality's role.[75]
Long-term developmental and health outcomes for offspring
Children conceived via assisted reproductive technology (ART) demonstrate long-term developmental outcomes that are generally comparable to those of naturally conceived peers, with cohort studies reporting no significant differences in cognitive, educational, or psychosocial adjustment through school age and into early adulthood.[82][83] A 2023 population-based analysis of primary school outcomes found no causal link between IVF conception and deficits in developmental or educational metrics after adjusting for confounders such as parental infertility and socioeconomic factors.[82] Similarly, a Japanese nationwide cohort study tracking children to age 9 identified no adverse effects on overall health or neurodevelopment attributable to IVF.[84]Physical health metrics in ART offspring show mostly reassuring patterns, though some evidence points to subtle elevations in cardiovascular and metabolic risks. Longitudinal follow-up of adults conceived via IVF revealed no differences in growth, respiratory function, or major metabolic markers compared to controls, but isolated studies have noted higher blood pressure, fasting glucose, and subcutaneous fat accumulation potentially linked to ART procedures.[85][86] A 2023 review of cohort data suggested possible increased risks for altered blood pressure and cardiovascular function, emphasizing the need for ongoing monitoring, though these may partly stem from underlying parental subfertility rather than ART itself.[22] Pubertal development appears unaffected, with a meta-analysis of multiple studies finding minimal interference in milestone achievement.[87]Epigenetic alterations represent a specific area of concern, with ART linked to a modestly elevated incidence of imprinting disorders such as Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Angelman syndrome, and Prader-Willi syndrome, potentially due to procedural disruptions in genomic imprinting during embryo culture or manipulation.[88][89] A 2024 assessment confirmed this association, estimating relative risks 2- to 11-fold higher for these rare conditions, though absolute incidences remain low (e.g., 4-11 per 10,000 ART births for Beckwith-Wiedemann).[89] However, broader epigenetic variations observed at birth, including DNA methylation changes, largely normalize by adulthood without evident impacts on health or development, as shown in a 2019 longitudinal profiling study.[90] Neurodevelopmental risks like autism spectrum disorder or cerebral palsy show inconsistent associations, with meta-analyses failing to confirm elevated odds after confounder adjustment.[91][92] Overall, while perinatal complications from ART contribute to early vulnerabilities, long-term data from registries and cohorts indicate resilience, underscoring the importance of distinguishing procedure-specific effects from those of infertility or multiplicity.[93][26]
Health risks and complications
Maternal and procedural risks
Assisted reproductive technology (ART) procedures, particularly in vitro fertilization (IVF), carry procedural risks primarily during ovarian stimulation and oocyte retrieval. Ovarian hyperstimulation syndrome (OHSS), resulting from exaggerated ovarian response to gonadotropins, affects 20-33% of IVF cycles with mild forms, 3-6% with moderate severity, and less than 1-5% with severe cases requiring intervention.[94][95] Severe OHSS can lead to ascites, hemoconcentration, thromboembolism, and renal impairment, with incidence reduced to under 5% in recent protocols through strategies like GnRH agonist triggering.[96] Oocyte retrieval, typically transvaginal under ultrasound guidance and sedation, involves risks of bleeding (0.2-1%), infection (0.1-0.5%), and rare visceral injury to bowel, bladder, or vessels (<0.1%).[97][98] Anesthesia-related complications, such as allergic reactions or respiratory issues, occur in fewer than 0.5% of cases.[99]Maternal risks extend into the pregnancy phase, exacerbated by ART-induced factors like multiple embryo transfers. Multiple gestations, historically comprising 20-30% of ART pregnancies before single-embryo transfer policies, elevate risks of preeclampsia (2-3-fold increase), gestational diabetes, anemia, and preterm labor compared to singletons.[100][101] ART-conceived pregnancies show a 1.71-fold higher preeclampsia risk versus spontaneous conceptions, independent of plurality, potentially due to endometrial-embryo asynchrony or subfertility selection.[102][103] Hypertensive disorders of pregnancy occur at higher odds in IVF/ICSI cycles, with odds ratios of 1.5-2.0 in meta-analyses.[103] Cesarean delivery rates exceed 50% in ART multiples, linked to malpresentation and maternal morbidity like hemorrhage.[100] Placental abruption risk is elevated (OR 2.14) in ART pregnancies.[104] These outcomes persist even after adjusting for maternal age and parity, though elective single-embryo transfer has mitigated multiple gestation rates to under 10% in many centers since 2010.[100]
Perinatal and childhood risks
Children born through assisted reproductive technology (ART) exhibit elevated perinatal risks compared to those conceived spontaneously, even among singletons after adjustment for confounders such as maternal age and parity. Preterm birth rates are higher, with adjusted relative risks ranging from 1.4 to 2.0 for delivery before 37 weeks gestation and 1.7 to 3.1 for very preterm birth before 32 weeks.[105] Low birth weight occurs more frequently, with adjusted risks of 1.6 to 1.7 for infants under 2500 grams.[105] Preeclampsia risk is increased by 71%, with a pooled relative risk of 1.71 across multiple studies.[106] Congenital malformations are also more common, showing an adjusted relative risk of 1.41.[105]These perinatal complications contribute to higher neonatal morbidity, including increased perinatal mortality (adjusted risks 1.7–2.0) and specific defects like congenital heart anomalies (odds ratio 1.55).[105] Although multiple embryo transfers historically amplified risks through higher twin rates, singleton ART pregnancies retain independent associations with adverse outcomes, potentially linked to procedural factors like ovarian stimulation or embryo culture conditions rather than solely underlying subfertility.[22]In childhood, ART offspring face modestly elevated risks for certain developmental and health issues, though many studies indicate overall similarity to spontaneously conceived peers after accounting for perinatal factors. Birth defects persist as a concern, with consistent evidence of increased incidence.[22] Neurodevelopmental outcomes, including cerebral palsy, show diminished excess risk in recent cohorts due to improved practices like single embryo transfer, while cognitive development and autism spectrum disorders display mixed findings without uniform elevation.[22] Cardiovascular markers, such as altered blood pressure and function, appear heightened in some follow-up studies.[22]Long-term cancer risk shows no overall increase for ART-conceived children, with hazard ratios near 1.0 for fresh and frozen embryo transfers compared to natural conception; however, subtype analyses reveal potential elevations in acute lymphoblastic leukemia (hazard ratio 1.61 for frozen transfers).[107] Mental and emotional health outcomes remain reassuringly comparable to the general population.[83] Ongoing research emphasizes the need to disentangle ART-specific effects from those of parental infertility, as subfertile couples without ART also exhibit slightly higher offspring risks in some domains.[22]
Potential epigenetic and long-term genetic effects
Assisted reproductive technologies (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), have been associated with epigenetic alterations in offspring, primarily involving changes in DNA methylation patterns at imprinted loci. These modifications arise from procedural elements such as ovarian hyperstimulation, embryo culture media, and micromanipulation techniques that bypass natural gamete selection. A 2022 study of cord blood from ART-conceived newborns revealed widespread DNA hypomethylation across the genome compared to naturally conceived controls, coinciding with the developmental window when epigenetic reprogramming occurs.[19] Such changes may disrupt genomic imprinting, where parental allele-specific methylation regulates gene expression, potentially leading to disorders like Beckwith-Wiedemann syndrome (BWS), characterized by overgrowth and tumor predisposition. Meta-analyses confirm an elevated relative risk of imprinting disorders, including BWS, in ART offspring, with approximately 4% of BWS cases linked to ART despite its rarity (incidence ~1 in 13,700 live births overall).[108][109][110]The absolute risk remains low, and confounding factors like underlying parental infertility complicate attribution solely to ART procedures. For BWS, the relative risk in ART-conceived children is estimated at 10.7-fold higher than in non-ART populations, though epidemiological data suggest this translates to an absolute increase from ~83 to ~888 cases per million births. Similar associations exist for Angelman syndrome, but large cohort studies indicate no consistent elevation in other imprinting defects like Prader-Willi syndrome. Genome-wide analyses show ART-specific methylation differences at birth often resolve by adulthood, with limited evidence of persistent functional impacts on gene expression or health outcomes. Animal models, however, demonstrate that ICSI can induce transgenerational epigenetic defects in germ cells, raising concerns for heritable changes in humans, though prospective human data are sparse.[111][112][90]Long-term genetic effects are less clearly delineated, with ICSI linked to modestly higher rates of congenital malformations (adjusted odds ratio 1.57), particularly genitourinary and chromosomal anomalies, potentially due to selection of compromised sperm. Population-based studies of ART adults report no significant differences in metabolic, cardiovascular, or neurodevelopmental risks compared to naturally conceived peers, though subtle elevations in blood pressure and imprinting-related cancers warrant monitoring. A 2023 mouse study indicated ICSI-induced heritable defects persisting across generations, but human evidence for transgenerational genetic risks remains indirect and unproven, emphasizing the need for extended follow-up in ART cohorts to distinguish procedural effects from parental factors.[27][85][113] Overall, while epigenetic perturbations are detectable, their clinical significance appears limited, with most ART offspring exhibiting normal long-term health, though ongoing research is essential given the technologies' evolution.[91]
Ethical controversies
Moral status of embryos and discard practices
The human embryo, formed at fertilization when sperm and egg fuse, constitutes a distinct organism of the species Homo sapiens with a unique genetic identity separate from that of the gametes or parents.[114][115] This scientific assessment, drawn from embryological principles, holds that a new human life begins at this stage, as the zygote initiates self-directed development toward maturity, a process continuous with fetal, infant, and adult stages without qualitative ontological change.[116][117]Ethical evaluations of the embryo's moral status diverge sharply. Proponents of full personhood, often grounded in biological individuality and potentiality arguments, assert that embryos warrant protections equivalent to born humans from conception, viewing any intentional destruction as morally equivalent to homicide.[118] This perspective, advanced by organizations like the American College of Pediatricians, emphasizes the embryo's inherent human dignity irrespective of size, location, or dependency.[116] In contrast, utilitarian or gradualist frameworks, prevalent in some bioethics literature, attribute increasing moral value correlating with developmental milestones such as sentience (around 20-24 weeks gestation) or viability, deeming early embryos as possessing lesser or no independent rights and permissible for research or disposal if they confer greater societal benefits like infertility treatment or stem cell advances.[119][120] Critics of the latter, including first-principles reasoning from causal continuity of human development, argue it imposes arbitrary thresholds unsupported by empirical biology, potentially licensing selective devaluation based on utility.[115]In assisted reproductive technologies (ART), particularly in vitro fertilization (IVF), protocols routinely generate multiple embryos to optimize implantation success, resulting in surplus beyond immediate transfer needs. In the United States, estimates indicate over 1.2 million cryopreserved embryos in storage as of recent data, with annual IVF cycles producing embryos where approximately 85% fail to yield live births due to non-transfer or non-viability.[121][122] Disposition options for these surplus embryos, per guidelines from the American Society for Reproductive Medicine (ASRM), include continued cryopreservation, donation for reproductive use by others, donation for research, or destruction after informed consent and a reasonable retention period (often five years for unclaimed cases).[123][123] Globally, discard practices vary; surveys of embryologists show 66.4% handling discards on a case-by-case basis at varying times, often via thawing without transfer, though exact volumes remain underreported due to inconsistent tracking.[124]These discard practices intensify moral debates, as they entail the deliberate termination of embryos deemed non-viable or excess. For instance, of non-transferred embryos, only about 2.2% are explicitly slated for discard in some U.S. clinic surveys, with others awaiting donation (2.3%) or indefinite storage (4.5%), yet many ultimately face destruction when storage fees lapse or parental decisions shift.[125] Entities attributing full moral status to embryos, such as in the 2024 Alabama Supreme Court ruling equating IVF embryos to children under wrongful death statutes, contend that such practices equate to mass-scale loss of human life, with U.S. IVF generating hundreds of thousands of discarded embryos annually.[126] ASRM ethics opinions permit disposal under regulated conditions but acknowledge burdens on clinics from unclaimed embryos, recommending policies to mitigate ethical conflicts without mandating absolute preservation.[123][127] Emerging efforts, like predictive algorithms to minimize excess embryo creation, aim to reduce discards but do not resolve underlying status disputes.[128]
Selection practices and eugenics concerns
Preimplantation genetic testing (PGT) enables the selection of embryos during in vitro fertilization (IVF) cycles by screening for genetic and chromosomal abnormalities prior to transfer. This involves biopsying the trophectoderm of blastocyst-stage embryos and analyzing extracted DNA for conditions such as monogenic disorders (PGT-M), aneuploidy (PGT-A), or structural rearrangements (PGT-SR).[129][130] PGT-M targets known familial risks, allowing avoidance of embryos carrying mutations like those for cystic fibrosis or Huntington's disease, while PGT-A aims to identify euploid embryos to potentially reduce miscarriage rates, though randomized trials have shown mixed efficacy, with some indicating no increase or even reduced live birth rates per cycle.[131][132]Usage of PGT has expanded globally, driven by technological advances in next-generation sequencing. In the United States, PGT-A application in IVF cycles is increasing, comprising a significant portion of procedures at specialized clinics, though exact national penetration rates vary by patient demographics and clinic protocols. The global PGT market was valued at approximately $0.7 billion in 2023, reflecting broader adoption in Europe via consortia like ESHRE, where data from 2023 cycles highlight trends in monogenic and chromosomal testing.[59][133][134] Non-medical applications, such as sex selection via PGT, are permitted in the U.S. for family balancing under guidelines from the American Society for Reproductive Medicine (ASRM), which deem it ethically acceptable absent IVF indications otherwise, though not all clinics offer it.[135] In contrast, many countries prohibit non-medical sex selection, with permissive regimes limited to the U.S. and select locations like Mexico.[136]Eugenics concerns arise from PGT's potential to extend beyond disease prevention to trait selection, evoking historical negative eugenics practices aimed at curtailing reproduction among those deemed genetically inferior. Critics argue that routine aneuploidy screening and emerging polygenic embryo selection (PES) for traits like intelligence or height foster "private eugenics," where parents privately engineer offspring, potentially exacerbating social inequalities and devaluing lives with disabilities.[137] Surveys of U.S. publics, clinicians, and patients reveal widespread apprehension that PES promotes eugenic thinking, distinguishing conditions (e.g., Down syndrome) from traits but still viewing selection against the former as discriminatory.[138] Proponents counter that PGT empowers informed parental choice and reduces suffering from severe heritable disorders, yet ethicists note the slippery slope: as genetic data proliferate, non-therapeutic selections could normalize discarding embryos for polygenic risks, mirroring early 20th-century coercive policies but decentralized through market-driven ART.[139][140] Empirical data on outcomes remain limited, with no large-scale studies quantifying societal impacts, underscoring the tension between individual reproductive autonomy and collective genetic diversity.[137]
Surrogacy, commodification, and family impacts
Surrogacy in assisted reproductive technology involves a woman carrying and giving birth to a child for intended parents, typically using gestational surrogacy where the surrogate has no genetic relation to the child via embryo transfer. Ethical critiques center on the potential for commodification, where human reproduction is treated as a market transaction, raising concerns about the intrinsic value of children and women's reproductive labor. Philosophers and bioethicists argue that payments to surrogates—often ranging from $20,000 to $50,000 in the United States—incentivize the outsourcing of gestation, akin to renting a womb, which undermines the non-commercial nature of human bonds and risks viewing offspring as products.[141][142] This perspective draws from first-principles reasoning that biological processes tied to identity and kinship should not be alienated for profit, as evidenced by disputes in surrogacy contracts where intended parents reject imperfect outcomes, such as disabilities, leading to legal battles over custody.[143]Commercial surrogacy amplifies commodification risks, particularly in low-regulation environments. In developing countries like Ukraine and India (prior to its 2022 ban on foreign surrogacy), economic disparities drive women into surrogacy for payments equivalent to years of local wages, often under coercive conditions including inadequate medical screening and confinement in surrogacy hostels. Reports document exploitation, such as surrogates facing withheld payments, forced cesareans, or abandonment if complications arise, with over 150 Ukrainian women applying monthly due to poverty.[144][145][146] Altruistic surrogacy, while avoiding direct payment, can still exploit familial or social pressures, as surrogates may forgo compensation yet bear disproportionate physical and emotional burdens without equivalent agency. Empirical data from global markets indicate higher preterm birth rates (up to 11.5% in singletons) and multiple gestations (2.6-75%), correlating with intensified medical interventions that prioritize intended parents' preferences over surrogate health.[147][148] These patterns suggest causal links between market incentives and health commodification, though pro-surrogacy advocates counter that informed consent mitigates harms—a claim contested by evidence of power imbalances in contracts favoring commissioning parties.[143][149]Impacts on family structures reveal mixed but concerning outcomes, with limited long-term data underscoring research gaps. Children born via surrogacy show comparable short-term psychological adjustment to peers in other assisted reproduction families, with low rates of emotional or behavioral disorders in U.S. studies of young children.[150] However, longitudinal evidence is inconclusive, particularly for identity formation; adults from traditional surrogacy report potential confusion over origins, and donor-conceived children in surrogacy often face disclosure challenges, with 90% of informed 10-year-olds in UK studies expressing curiosity about surrogates yet minimal contact (28% seeing them yearly).[151][152][153] Surrogates experience elevated mental health risks, including higher postpartum depression and new diagnoses during pregnancy compared to non-surrogate mothers, potentially from disrupted bonding or grief over separation—contradicting claims of emotional neutrality.[154][155] Intended parents report satisfaction but face relational strains from legal uncertainties and surrogate involvement, with family well-being post-surrogacy rated highly by 86.6% of surrogates in one survey yet shadowed by unresolved ethical tensions over non-traditional kinship.[156] Overall, while some data indicate resilience, the causal realism of outsourcing gestation challenges conventional family bonds, warranting caution given academia's tendency to minimize disruptions in pro-ART literature.[157][158]
Legal and regulatory landscape
International principles and variations
The absence of a comprehensive binding international treaty on assisted reproductive technology (ART) leaves regulation to national frameworks, informed by soft law instruments from organizations such as the World Health Organization (WHO), UNESCO, and the Council of Europe. The WHO recognizes ART, including in vitro fertilization (IVF), as a valid treatment for infertility affecting approximately 17.5% of adults globally, but emphasizes equitable access, safety, and ethical oversight without prescriptive rules.[159] UNESCO's International Bioethics Committee (IBC) report on ART and parenthood underscores principles like human dignity, informed consent, non-commercialization of reproductive materials, and the child's best interests, advocating against practices that commodify human life or undermine family structures.[160] Similarly, the Council of Europe's Oviedo Convention (1997), ratified by 29 countries as of 2023, prohibits harmful genetic interventions and embryo research beyond 14 days, prioritizing protections for human dignity and physical integrity in biomedical applications, though non-ratifiers like the United Kingdom pursue more flexible policies.[161]Global variations reflect cultural, religious, and ethical divergences, with policies categorized broadly as permissive, restrictive, or prohibitive. Permissive jurisdictions, such as the United States and Australia, impose limited federal constraints, allowing practices like preimplantation genetic diagnosis (PGD), egg donation, and gestational surrogacy under professional guidelines from bodies like the American Society for Reproductive Medicine (ASRM), which recommends single embryo transfer to minimize risks but lacks enforcement power.[162] In contrast, restrictive European nations like Germany (Embryo Protection Act, 1990) and Italy (Law 40/2004, partially amended) ban embryo cryopreservation, egg donation, and multiple embryo creation per cycle to affirm the moral status of embryos from fertilization, limiting IVF to fresh cycles with strict age caps (e.g., women under 50 in Italy).[163] Prohibitive stances prevail in several Muslim-majority countries, where 14 surveyed nations (as of 2019) permit IVF only using gametes from legally married couples, explicitly forbidding donor gametes, surrogacy, and sex selection to align with Islamic prohibitions on third-party genetic contributions and lineage purity.[164]The International Federation of Fertility Societies (IFFS) surveillance reports document these disparities, noting that by 2019, ART was available in over 100 countries but with heterogeneous rules on donor anonymity (mandatory disclosure in Sweden since 1985, anonymity preserved in Japan), gestational limits (e.g., no transfers after age 50 in France), and funding (public reimbursement in Denmark covering up to six cycles, versus privatized access in the U.S.).[165] Such variations influence utilization rates and ethical debates, with permissive systems enabling higher volumes (e.g., 2.5% of U.S. births from ART in 2021) but raising concerns over unmonitored multiple births, while restrictive models prioritize embryo protection at the cost of accessibility.[166] Cross-border reproductive care, or "fertility tourism," emerges as a consequence, with patients from restrictive nations seeking services in permissive ones like Spain or Cyprus.[167]
Restrictive vs. permissive national policies
National policies on assisted reproductive technology (ART) diverge significantly between restrictive and permissive approaches, with the former emphasizing embryo protection, ethical constraints on selection practices, and limits on procedures to reduce risks like multiple gestations, while the latter prioritizes broad access, innovation, and patient choice with minimal federal oversight.[168] Restrictive frameworks often prohibit or tightly regulate preimplantation genetic diagnosis (PGD), embryo cryopreservation beyond immediate use, gamete donation anonymity, and surrogacy, aiming to prevent commodification and align with moral views on human life from conception.[162] In contrast, permissive policies enable wider use of advanced techniques like PGD for aneuploidy screening, commercial surrogacy, and anonymous donation, often resulting in higher utilization rates but raising concerns over embryo discard volumes and long-term safety data gaps.[168]Germany exemplifies restrictive regulation through its 1990 Embryo Protection Act, which bans creating embryos for research or surplus, limits fertilization to three oocytes per cycle for immediate transfer only, and permits PGD solely for preventing grave hereditary diseases, with violations punishable by up to five years imprisonment.[168] Italy's Law 40 of 2004 initially imposed similar oocyte limits and banned cryopreservation, leading to elevated multiple pregnancy rates (around 20% before amendments); partial reforms in 2009 and 2014 allowed cryopreservation and expanded PGD access, but surrogacy remains prohibited nationwide, with penalties including imprisonment.[162] Other restrictive nations include Austria and France, where PGD is confined to severe genetic risks, and full bans on IVF persist in countries like the Philippines and Costa Rica, citing ethical objections to embryo manipulation.[169] These policies correlate with lower ART cycle volumes per capita—e.g., Germany's 8.5 cycles per 1,000 women aged 15–44 in 2016—potentially reducing ethical issues but constraining options for older patients or those with genetic risks.[168]Permissive regimes, such as in the United States, operate without overarching federal ART laws, deferring to state regulations and professional guidelines from bodies like the American Society for Reproductive Medicine (ASRM), enabling routine PGD for chromosomal abnormalities, embryo sex selection in some clinics, and commercial surrogacy in states like California, where pre-birth parentage orders enforce contracts.[162] This yields high activity, with over 2 million ART cycles reported cumulatively by 2016 via the CDC's national registry, though decentralized enforcement leads to variability, such as surrogacy bans in states like New York until 2020 reforms.[162] Israel provides another model, funding up to two children via unlimited IVF cycles for women aged 18–45 (publicly covering PGD for medical indications), permitting regulated gestational surrogacy since 1996, and allowing embryo research under strict oversight, driving one of the world's highest per capita rates at 20.6 cycles per 1,000 women in 2016.[168] Spain, while banning surrogacy, permits broad PGD authorization, anonymous oocyte donation until 2019 reforms mandated non-anonymity, and no strict age caps, supporting cross-border reproductive care with 14,747 donor cycles in 2016.[168]
Country
Key Restrictive Features
Key Permissive Features
Germany
No surplus embryos; PGD limited to severe diseases; no surrogacy
IVF access for heterosexual couples; state funding up to age 40
PGD for monogenic disorders; cryopreservation allowed
United States
State-level variations; no federal embryo limits
PGD widespread; commercial surrogacy in select states
Israel
Egg donor age caps (21–35); no embryo donation
Unlimited public IVF funding to two children; surrogacy regulated
Spain
Surrogacy illegal; limited public cycles (3 max)
PGD authorized; oocyte donation open to singles/lesbians
Such contrasts influence outcomes: restrictive policies in Europe have lowered multiple birth rates to under 10% via single-embryo transfer mandates, versus higher rates in less regulated settings pre-guidelines, though permissive access expands equity for non-traditional families while amplifying debates on embryo viability selection.[162][168]
Access, funding, and enforcement issues
Access to assisted reproductive technology (ART) remains uneven globally, with high costs serving as the primary barrier, often exceeding $15,000 per IVF cycle in the United States before medications.[170] Socioeconomic status profoundly influences utilization, as individuals from lower-income households are less likely to pursue treatment; for instance, in the U.S., the majority of ART users earn over $100,000 annually and hold higher education levels, while those in the lowest socioeconomic quartiles represent under 25% of cycles despite similar infertility prevalence.[171][172] Racial and ethnic disparities exacerbate this, with Black and Hispanic women facing reduced access due to factors including insurance gaps and clinic availability, leading to lower live birth rates even when treatment is initiated.[173] Geographic barriers compound inequities, particularly in rural areas or regions with few specialized centers, where travel distances can exceed 60 minutes, deterring initiation of care.[174][175]Funding models vary widely by jurisdiction, with public insurance covering ART in select European countries but largely absent elsewhere. In Denmark, public health services fund up to three IVF cycles for patients under 40 seeking their first child, while Israel's national system provides partial coverage without marital status restrictions.[176] In contrast, the U.S. lacks federal mandates, relying on state-level insurance requirements in only 21 states as of 2023, which often exclude IVF or cap cycles, leaving most costs out-of-pocket or reliant on employer benefits.[177] Medicaid, the primary public program for low-income Americans, covers infertility diagnostics in limited states but rarely ART procedures, perpetuating access tied to private wealth.[178] Globally, lower-middle-income countries exhibit minimal public funding, with patients bearing full expenses amid inadequate infrastructure, resulting in utilization rates below 1% of infertile couples compared to 2-5% in high-income nations.[179]Enforcement of ART regulations faces challenges, particularly with cross-border practices evading national bans. Surrogacy, prohibited in countries like Germany and Austria for ethical reasons including commodification concerns, prompts "reproductive tourism" to permissive jurisdictions such as Ukraine or Georgia, complicating parentage recognition and child welfare upon return.[180] In the U.S., state variations lead to enforcement gaps; for example, New York's 2021 Child-Parent Security Act permits compensated gestational surrogacy but voids traditional arrangements as against public policy, yet interstate disputes arise over contracts formed elsewhere.[181][182] India's 2021 Assisted Reproductive Technology Act imposes strict licensing and bans commercial surrogacy to curb exploitation, but underground markets persist due to weak monitoring, with reports of non-compliance in unregistered clinics.[180] Overall, inconsistent international enforcement undermines uniform standards, raising risks of substandard care and legal voids in parentage establishment.[162]
Global usage and trends
Utilization statistics and growth patterns
Over 3 million assisted reproductive technology (ART) cycles are performed annually worldwide, according to data compiled by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) for 2022, yielding approximately 770,000 live births.[73] Cumulatively, an estimated 10 to 13 million babies have been born through ART from 1978 through 2018, with preliminary figures indicating several million additional births in the subsequent years amid rising demand. [183] This growth reflects broader trends in infertility prevalence, affecting roughly 1 in 6 adults globally, compounded by delayed childbearing and improved access in permissive regulatory environments.[184]In the United States, ART utilization has expanded markedly, with reported in vitro fertilization (IVF) cycles increasing from 389,993 in 2022 to 432,641 in 2023 across 371 clinics, resulting in 95,860 live births—the latter representing about 2.7% of total U.S. births that year.[5] This marks an over twofold rise in cycles since 2011, driven by technological refinements and greater societal acceptance, though live birth rates per cycle remain below 50% overall, varying by maternal age.[67] In Europe, ART accounts for 3% to 9% of national births, with Spain reporting the highest proportion at nearly 9% as of recent data, followed by countries like Greece and Denmark; European cycles totaled over 900,000 in 2019, showing steady annual increments despite regulatory variations.[185][186]Asia exhibits rapid uptake in select nations, exemplified by Japan, where 77,200 ART live births occurred in 2022, predominantly from frozen embryo transfers amid government subsidies promoting fertility treatments.[187] Globally, the ART sector's market value, proxying demand and investment, grew from approximately USD 25 billion in 2023 toward projected expansion at 7% compound annual growth rate through 2030, fueled by innovations like preimplantation genetic testing and intracytoplasmic sperm injection, which have boosted success rates over time.[188][189] However, underreporting in low-resource regions limits comprehensive global tallies, with ICMART estimates suggesting actual cycles may exceed reported figures by 20-30%.[166]
Region/Country
Estimated Annual Cycles (Latest Available)
Live Births (Latest Available)
Notes on Growth
Worldwide
>3 million (2022)
~770,000 (2022)
Steady rise since 1978; demand exceeds supply by factor of 3-7.[73][166]
High volume due to policy support; FET dominant.[187]
Demographic and socioeconomic profiles
Users of assisted reproductive technology (ART) are disproportionately older than the general childbearing population, with the average age of patients in the United States reported as 36.3 years in 2021 data from the Centers for Disease Control and Prevention (CDC).[63] This skew reflects underlying infertility patterns, as fertility declines with age, prompting delayed childbearing among career-oriented or educationally advanced individuals to seek ART interventions like in vitro fertilization (IVF). Internationally, similar age profiles emerge; for instance, in a Canadian study of ART-conceived parents, those using the technology were notably older than naturally conceiving counterparts.[190]Racial and ethnic disparities characterize ART utilization in the United States, where White patients comprise the majority of cycles, while Black and Hispanic women exhibit lower uptake rates. Analysis of Society for Assisted Reproductive Technology (SART) data from 2016–2019 showed preimplantation genetic testing for aneuploidy (PGT-A) usage at 33% among White women, 24% among Black women, 31% among Hispanic women, and 44% among Asian women, indicating varied access or preferences influenced by cultural, economic, or systemic factors.[191] These patterns persist despite comparable infertility prevalence across groups, suggesting barriers beyond biology, including distrust in medical systems or geographic availability, as documented in reviews of U.S. ART access.[192]Socioeconomically, ART patients tend toward higher education and income levels, reflecting the high costs of procedures—often exceeding $15,000 per IVF cycle in the U.S. without insurance coverage—which limit access for lower-income groups. Studies confirm that parents of ART-conceived children are more likely to hold advanced degrees and reside in affluent areas; for example, a Canadian cohort found ART users overrepresented among those with the highest income and education quintiles.[190]Marital status further delineates profiles, with married heterosexual couples dominating usage, comprising the bulk of cycles, while single women and same-sex couples represent smaller but growing shares amid expanding legal recognitions.[173] Disparities exacerbate inequities, as lower socioeconomic status correlates with reduced ART initiation and success rates, independent of clinical factors, per analyses linking community income to cumulative live birth probabilities.[193]
Barriers to access and equity concerns
Financial barriers represent the primary obstacle to assisted reproductive technology (ART), with a single in vitro fertilization (IVF) cycle costing between $12,000 and $25,000 in the United States, often without comprehensive insurance coverage outside of a minority of states that mandate it.[194][195] Globally, costs vary significantly, ranging from €2,100 to €3,500 in select Eastern European countries to higher figures in Western nations, driving medical tourism but exacerbating inequities for those unable to travel.[196] These out-of-pocket expenses, coupled with low success rates requiring multiple cycles (averaging $50,000 total per patient), limit utilization primarily to higher-income households, where ART accounts for up to 6.2% of births in the top income quartile compared to 1.4% in the lowest.[194][197]Socioeconomic disparities persist even in systems with subsidized or free ART, as evidenced by a 15.8% decrease in access across progressively disadvantaged quintiles in Australia and strong social gradients in France despite no direct costs to patients.[198][175]In the United States, lower utilization correlates with reduced education, income, and ethnic minority status, with non-HispanicBlack and Hispanic women facing compounded barriers including clinic availability and implicit biases in provider recommendations, though data attributes much of the gap to economic factors rather than overt discrimination.[173][199] Geographic remoteness further hinders access, particularly in rural areas or developing countries where infrastructure and specialist distribution are inadequate, resulting in ART contributing to only 1.5% of U.S. births versus 3% in Europe.[174][173]Regulatory restrictions amplify equity concerns by excluding groups based on marital status, sexual orientation, or age in over half of European countries, where prohibitions on single or same-sex access prevail, and in nations like those influenced by religious doctrines where IVF is outright banned.[200][201] Age caps, such as 42 in Sweden or 50 in parts of Europe, ration resources but disproportionately affect older infertile individuals who may otherwise succeed biologically.[176] Globally, the World Health Organization estimates infertility impacts one in six people, yet access remains insufficient in low-resource settings due to absent socio-cultural support and economic prerequisites, perpetuating a divide where high-income nations achieve higher ART penetration while developing regions lag.[202][203] These barriers underscore causal links between policy, economics, and biology, where unaddressed disparities not only delay family formation but also correlate with elevated mental health burdens, including a 48% higher antidepressant prescription rate among prolonged infertile women.[195]
Societal and cultural dimensions
Shifts in family and reproduction norms
Assisted reproductive technologies (ART), particularly in vitro fertilization (IVF) introduced in 1978, have decoupled biological reproduction from sexual intercourse and traditional marital unions, enabling parenthood for infertile heterosexual couples, single individuals, and same-sex partners.[204] This shift challenges historical norms where reproduction was inherently tied to coital acts within opposite-sex marriages, fostering diverse family configurations such as single-mother-by-choice households via sperm donation and two-mother families through reciprocal IVF.[205] Empirical data indicate that ART utilization by non-heterosexual and unmarried individuals has risen, with clinics reporting increased requests from these groups, reflecting a normative evolution toward viewing biological relatedness as optional or substitutable by intention and social bonds.[206]In parallel, ART has normalized delayed childbearing and advanced parental age, reducing childlessness rates among women over 35 by compensating for age-related fertility declines, though overall fertility rates remain influenced by broader postponement trends.[207] For instance, projections suggest that up to 10% of children in developed nations may soon be conceived via IVF, amplifying the prevalence of donor-conceived offspring who lack genetic ties to one or both social parents.[208] Single women and lesbian couples increasingly access sperm donation for ART, with comparable success rates to heterosexual counterparts, while single and coupled gay men achieve live birth rates exceeding 85% through egg donation and gestational surrogacy.[209] These practices redefine kinship, introducing concepts like "genetic strangers" as progenitors and prompting legal reevaluations of parentage presumptions traditionally anchored in marriage.[210]Such innovations have prompted societal reevaluation of family ideals, with ART facilitating "instant families" via third-party reproduction that prioritize reproductive autonomy over conventional genetic continuity.[211] Critics argue this commodifies gametes and gestation, potentially eroding norms emphasizing paternal investment and dual biological parentage, as evidenced by rising numbers of children in single-parent or non-genetic households—over 95,000 U.S. babies born via IVF in 2023 alone, many in non-traditional setups.[5][212] Nonetheless, longitudinal studies of ART families often report stable parenting quality comparable to natural conception families, though gaps persist in data on long-term child outcomes amid donor anonymity debates.[213] Globally, these trends correlate with cultural acceptance of diverse reproduction pathways, yet they coexist with persistent barriers in restrictive jurisdictions, underscoring uneven normative shifts.[214]
Psychological effects on parents and children
Parents undergoing assisted reproductive technology (ART) often experience elevated levels of stress, anxiety, and depression during the treatment process, with meta-analyses indicating that pretreatment psychological distress can predict lower success rates in procedures like in vitro fertilization (IVF).[215] However, following successful live births, many report improved psychological well-being, including reduced trait anxiety among fathers and overall family satisfaction comparable to or exceeding that of naturally conceiving parents.[216] Longitudinal studies show that while infertile couples without children exhibit rising psychopathological symptoms over time, those achieving parenthood through ART demonstrate resilience, with maternal mental health stabilizing or enhancing across pregnancy trimesters despite initial strains from hormonal treatments and uncertainty.[217][218]For donor-conceived parents, decisions around disclosure to children can introduce ongoing emotional challenges, potentially complicating family dynamics if withheld, though empirical evidence links early, age-appropriate disclosure with better parental adjustment and reduced secrecy-related guilt.[219] Multiple births from ART, which occur at higher rates than in spontaneous conceptions, may amplify parental stress due to intensified caregiving demands, yet post-adjustment outcomes typically align with those of parents of naturally conceived multiples when controlling for socioeconomic factors.[220]Children conceived via ART exhibit long-term psychological outcomes broadly equivalent to those of spontaneously conceived peers, with large cohort studies finding no elevated risk of psychiatric disorders, including anxiety, depression, or attention-deficit/hyperactivity disorder, into adolescence.[221][222] Systematic reviews confirm that ART offspring display similar cognitive, emotional, and behavioral adjustment from early childhood through young adulthood, often benefiting from enriched family environments characterized by high parental investment.[157][223] Parent-child attachment remains secure in most cases, persisting positively into adolescence regardless of conception method.[224]Donor-conceived children generally report psychological adjustment on par with non-donor peers, with meta-analyses showing no consistent links to diminished mental health, identity disturbances, or lower quality of life, though some express curiosity about genetic origins that correlates with secure parental attachment rather than distress.[225] Insecure attachment patterns, such as disorganization, appear more tied to negative perceptions of the donor or family stressors than to the mode of conception itself, underscoring the role of parental communication and support in mitigating potential vulnerabilities.[226][227] While some studies note slightly higher autism spectrum disorder risks in ART cohorts, these are often attributable to underlying parental infertility factors rather than the technology, with overall reassuring profiles when isolated from confounders like prematurity.[22]
Representations in media and public discourse
In popular media, assisted reproductive technologies (ART) are frequently portrayed through narratives emphasizing emotional triumphs over infertility, though often with dramatized ethical tensions. Films such as Private Life (2018) depict the strains of in vitro fertilization (IVF) cycles, including hormonal effects and relational stress, drawing from real patient experiences while compressing timelines for dramatic effect.[228] Television series like Friends (1994–2004) present surrogacy positively via Phoebe Buffay's gestational role, focusing on altruism and bonds but glossing over contractual risks and post-birth attachments.[229] Dystopian works, including The Handmaid's Tale (2017–present), reframe surrogacy as state-enforced exploitation, amplifying public fears of commodified reproduction amid declining natural fertility rates.[230] These depictions, while engaging, tend to prioritize individual agency over empirical success rates, which hover around 30–40% per IVF cycle for women under 35, per clinic data.[231]News coverage of ART often spotlights celebrity usages and anomalies, shaping perceptions toward accessibility despite high costs averaging $15,000 per IVF attempt in the U.S.[232] High-profile cases, such as those involving actors like Kim Kardashian or Elon Musk disclosing surrogacy in 2021–2022, normalize the practice for affluent demographics but rarely address socioeconomic barriers, with only 1–2% of U.S. births involving ART annually.[232] Sensational stories, including international surrogacy scandals in Ukraine and India pre-2018 bans, highlight exploitation risks, such as surrogates housed in dormitories under agency control, fueling discourse on child trafficking and maternal health vulnerabilities.[233] Content analyses of North American newspapers from 2000–2010 reveal framing that balances optimism with cautions on older maternal risks, like chromosomal anomalies rising post-40, yet underreports long-term child outcomes amid media incentives for feel-good narratives.[234]Public opinion polls indicate broad endorsement of ART, particularly IVF, with 70% of Americans in a 2024 Pew survey deeming access a "good thing" and 80% supporting its legality, though familiarity has grown to 42% knowing users by 2023, up from 33% in 2018.[235][236] Support wanes for specifics like embryo selection or posthumous reproduction, with surveys showing 55% favoring insurance mandates but 89% rejecting infertility as a "disease," reflecting causal views tying reproduction to age-related biology rather than pathology.[237] Cross-national data, including European attitudes, align with U.S. trends, favoring public funding for IVF but scrutinizing gamete donation due to kinship disruptions.[238]Ethical debates in discourse critique ART's commercialization, projected to exceed $37 billion globally by 2027, arguing it incentivizes embryo surplus (averaging 5–10 per cycle) and discards, conflicting with pro-life perspectives on fetal viability from 8 weeks gestation.[239]Surrogacy draws particular ire for potential exploitation, as in Swedish journalistic analyses (2009–2019) framing it as rights competition between intending parents and gestational carriers, with evidence of uneven bargaining in low-regulation markets.[240] While media and academic sources often advocate permissive policies, empirical reviews underscore unresolved child welfare gaps, such as identity issues in donor-conceived offspring, prompting calls for registry mandates absent in most jurisdictions.[9] These tensions persist, with post-2022 Alabamaembryo rulings amplifying U.S. divides over ART's intersection with abortionethics.[241]
Recent advancements and future directions
Integration of AI and non-invasive technologies
Artificial intelligence (AI) has been increasingly integrated into assisted reproductive technology (ART) processes, particularly for embryo selection and outcome prediction, leveraging machine learning algorithms trained on large datasets of imaging and clinical variables. In embryo assessment, AI models analyze time-lapse microscopy videos to classify blastocyst viability, achieving median accuracies of 75.5% in predicting morphological grades compared to embryologist evaluations.[242] Clinical trials have demonstrated that AI-assisted selection can yield clinical pregnancy rates of 46.5% to 61.0%, comparable to or slightly exceeding traditional morphology-based methods, with some reports indicating 15-20% improvements in overall IVF success rates through reduced multiple embryo transfers and enhanced implantation predictions.[243][244][245]AI extends to personalization of ovarian stimulation protocols by processing patient-specific data such as age, hormone levels, and prior cycle outcomes to optimize gonadotropin dosing, potentially increasing oocyte yield while minimizing risks like ovarian hyperstimulation syndrome.[246] In intracytoplasmic sperm injection (ICSI), AI algorithms identify optimal injection sites on oocytes and confirm membrane breakage, standardizing procedures that traditionally rely on operator expertise.[247] These applications, validated in studies from 2023-2025, underscore AI's role in reducing subjectivity, though challenges persist in achieving over 80-90% predictive accuracy for live births due to data variability and the need for larger, diverse validation cohorts.[248][249]Non-invasive technologies complement AI by enabling embryo evaluation without biopsy, addressing concerns over potential cell damage from invasive preimplantation genetic testing (PGT). Non-invasive PGT for aneuploidy (niPGT-A) detects cell-free DNA in spent embryo culture medium (SCM), offering a biopsy-free alternative for chromosomal screening with emerging concordance rates to trophectoderm biopsy in blastocysts.[250] Recent advancements, including SCM-based next-generation sequencing validated in 2024-2025 studies, position niPGT-A as a backup or primary tool for prioritizing euploid embryos, potentially improving transfer success while preserving embryo integrity.[251][252]The synergy of AI and non-invasive methods is evident in multimodal assessments, where AI processes non-invasive data from metabolomics, Raman spectroscopy, or time-lapse imaging to predict viability without genetic sampling. For instance, AI-driven analysis of SCM biomarkers or embryo morphokinetics integrates with niPGT-A to refine selection criteria, aiming to boost live birth rates while minimizing ethical concerns over embryo manipulation.[253] Automated systems incorporating these technologies, such as AI-optimized incubators, enhance lab efficiency and consistency, though regulatory hurdles and the need for prospective randomized trials limit widespread adoption as of 2025.[50][254]
Genetic editing and stem cell innovations
Genetic editing technologies, particularly CRISPR-Cas9, have been explored for correcting genetic mutations in embryos during assisted reproductive technology procedures to prevent heritable disorders. In 2017, researchers at Columbia University used CRISPR to eliminate the gene associated with retinitis pigmentosa, a form of inherited blindness, from human embryos created via IVF, demonstrating potential for editing single-gene disorders without implantation.[255] However, studies have highlighted significant risks, including off-target mutations that could introduce unintended genetic changes, as evidenced by experiments in 2023 showing CRISPR-Cas9's inefficiency and error-prone nature in human embryos, prompting warnings against its clinical therapeutic use.[256] Applications in ART remain largely experimental, with potential to enhance embryo selection and reduce risks like mitochondrial DNA diseases, though regulatory restrictions in most countries limit germline editing to research only, due to concerns over long-term safety and ethical implications of heritable changes.[257][50]Stem cell innovations, including induced pluripotent stem cells (iPSCs), enable in vitrogametogenesis (IVG), the creation of functional gametes from somatic cells, addressing infertility in cases of gamete scarcity such as post-menopausal women or same-sex couples. In September 2025, Oregon Health & Science University (OHSU) researchers generated 82 functional oocytes from human skin cells reprogrammed into iPSCs, which were fertilized via IVF, marking a milestone in human IVG though not yet leading to live births.[258] Earlier animal models, including mice, have produced live offspring from iPSC-derived gametes, with human protocols advancing through differentiation into primordial germ cell-like cells followed by maturation into oocytes or sperm.[259] In May 2025, REPROCELL reported the world's first live birth using Fertilo, a stem cell-derived in vitrooocyte maturation system, which supports oocyte development outside the body to improve IVF outcomes for patients with immature eggs.[260] These approaches also include ovarian organoids engineered from stem cells to mimic follicular environments, potentially rejuvenating ovarian function in age-related infertility, though clinical translation faces hurdles like epigenetic fidelity and tumor risk from pluripotent cells.[261][262]Integration of genetic editing with stem cell-derived gametes holds promise for comprehensive infertility solutions, such as editing iPSC lines prior to gamete production to eliminate genetic defects, but ethical debates persist over safety, consent for future generations, and equitable access, with no widespread clinical adoption as of 2025.[263][50] Preclinical successes in non-human models, like sheep embryos edited via CRISPR post-IVF, indicate feasible scalability, yet human trials emphasize the need for rigorous validation to avoid mosaicism and ensure developmental viability.[264]
Emerging challenges and unresolved debates
One prominent unresolved debate centers on polygenic embryo screening (PES), which uses polygenic risk scores to select embryos with lower predicted risks for complex traits or diseases during IVF. Proponents argue it could reduce heritable conditions, but critics highlight its limited predictive accuracy—often capturing only 10-20% of trait variance due to environmental factors and gene-environment interactions—and potential for unintended eugenic outcomes, such as selecting for non-medical traits like intelligence.[265][266] Ethical concerns include infringing on the future child's autonomy and exacerbating social inequalities, as PES adds significant costs (up to $10,000 per cycle) not covered by insurance, limiting access to affluent users.[267] A 2024 survey found 70% of U.S. respondents supported PES for disease risk but opposed it for enhancement traits, underscoring publicambivalence.[268]Long-term health outcomes for ART-conceived children remain contentious, with empirical data indicating elevated risks independent of multiple gestations. A Swedish registry analysis of over 2.6 million births (1982-2007) showed ART children had a 1.5-fold increased asthma risk, persisting into adolescence.[93] Cardiovascular studies report higher blood pressure and metabolic alterations in ART offspring, potentially linked to epigenetic changes from in vitro culture or ovarian stimulation, though causality is debated as underlying parental infertility may confound results.[269] A 2022 review of cohort studies found no consistent increase in neurodevelopmental disorders but noted sparse data beyond early adulthood, calling for longitudinal monitoring amid rising ART use (now 2% of U.S. births).[270] These findings fuel debates on whether procedural risks justify widespread adoption without enhanced safety protocols.Commercial surrogacy raises exploitation allegations, particularly in low-regulation markets where socioeconomic disparities prevail. In developing countries, surrogates often earn $10,000-20,000 per pregnancy—far above local wages but tied to contracts with limited protections—prompting claims of commodifying women's bodies, as evidenced by reports of inadequate medical oversight and psychological coercion.[271][272] Defenders cite voluntary participation and empowerment via income, with U.K. data showing surrogates reporting high satisfaction and no bonding regrets post-birth, yet global bans (e.g., in parts of Europe) reflect unresolved tensions over child commodification and trafficking risks in cross-border arrangements, which comprise 10-20% of cases.[273][142]Socioeconomic barriers perpetuate inequity, with ART access correlating inversely with income and geography. In Australia, utilization dropped 15.8% across quintiles from highest to lowest socioeconomic status, despite public funding, due to indirect costs like travel and lost wages.[174] U.S. data reveal Black and Hispanic patients face 20-30% lower IVF initiation rates than whites, compounded by insurance gaps affecting 60% of cycles, raising debates on whether subsidies or mandates could address selection effects where ART amplifies higher-SES reproduction.[173][274] Regulatory fragmentation—lacking unified U.S. oversight unlike Europe's clinics—exacerbates commercialization risks, with the global ART market projected at $37.7 billion by 2027, prioritizing profit over standardized safety.[239] These challenges demand evidence-based reforms, balancing innovation against empirical harms.