Assessment of a Decade of Change in U.S. Assisted Reproductive Technology Cumulative Live-Birth Rates: 2004-2009 Compared With 2014-2020.

OBJECTIVE: To assess the effects of demographic shifts, changes in contemporaneous clinical practices, and technologic innovation on assisted reproductive technology (ART) success rates by conducting an analysis of cumulative live-birth rates across different time periods, age groups, and infertility diagnoses. METHODS: We conducted a retrospective cohort study of autologous linked cycles comparing cumulative live-birth rates over successive cycles from patients undergoing their first retrieval between 2014 and 2019 in the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) database. All cycles reported for these individuals up to 2020 were included for analysis. We compared cumulative live-birth rates stratified by age and infertility cause with published data from the 2004-2009 SART CORS database. RESULTS: From 2014 to 2019, 447,042 patients underwent their first autologous index retrieval, resulting in 1,007,374 cycles and 252,215 live births over the period of 2014 to 2020. In contrast, between 2004 and 2008, 246,740 patients underwent 471,208 cycles, resulting in 140,859 births by 2009. Noteworthy shifts in demographics were observed, with an increase in people of color seeking reproductive technology (57.9% vs 51.7%, P <.001). There was also an increase in patients with diminished ovarian reserve and ovulatory disorders and a decrease in endometriosis, tubal, and male factor infertility ( P <.001). Previously associated with decreased odds of live birth, frozen embryo transfer and preimplantation genetic testing showed increased odds in 2014-2020. Preimplantation genetic testing rose from 3.4% to 36.0% and was associated with a lower cumulative live-birth rate for those younger than age 35 years ( P <.001) but a higher cumulative live-birth rate for those aged 35 years or older ( P <.001). Comparing 2014-2020 with 2004-2009 shows that the overall cumulative live-birth rate improved for patients aged 35 years or older and for all infertility diagnoses except ovulatory disorders ( P <.001). CONCLUSION: This analysis provides insights into the changing landscape of ART treatments in the United States over the past two decades. The observed shifts in demographics, clinical practices, and technology highlight the dynamic nature of an evolving field of reproductive medicine. These findings may offer insight for clinicians to consider in counseling patients and to inform future research endeavors in the field of ART.

The future of surrogacy: a review of current global trends and national landscapes.

The practice of surrogacy is frequently the subject of media, scientific, social, regulatory and policy attention. Although it is, for many, an accepted form of assisted reproduction for those who would otherwise not be able to have children, surrogacy often generates strong feeling, particularly where there is any possibility of exploitation. Therefore, there is disagreement about how it should be regulated. In some countries, surrogacy is prohibited in any form, although this does not stop people using it. In others, it is unregulated but still practised. In some nations it is regulated in either a 'commercial' or an 'altruistic' model. This review article considers the possible regulatory future of surrogacy, initially from a UK perspective considering a recent review of the legal framework in a country where surrogacy works well (although some cross borders to access it), and then through an assessment of global trends and other national perspectives. It concludes that the international regulation of surrogacy, although potentially desirable, is unlikely. This being the case, it would be preferable for individual nations to regulate surrogacy so it can be undertaken in ways that are safe, ethical and protective of the best interests of children, surrogates, intended parents and families.

Trends and Outcomes of Assisted Reproductive Technology Cycles Using a Gestational Carrier Between 2014 and 2020.

This study used national surveillance data from the Society for Assisted Reproductive Technology to describe trends and outcomes in assisted reproductive technology cycles using a gestational carrier vs those not using a gestational carrier.

The ART of cryopreservation and its changing landscape.

The purpose of this review is to educate the reader on the role that cryopreservation has played and continues to play in the ever-evolving field of assisted reproductive technologies, specifically in clinical human fertility treatment. We discuss the science behind the cryopreservation methods and investigated some of the major considerations that any clinic or cryobank faces in terms of risks and liabilities, physical challenges that accompany the constantly growing collection of cryopreserved specimens, and what this means on the ethical and legal front. Finally, we take a glimpse in the future to explore what may be on the horizon for the preservation of gametes and reproductive tissues.

Hospitalizations up to 8 years following delivery in assisted reproductive technology-treated and subfertile women.

OBJECTIVE: To investigate hospitalizations up to 8 years after live birth among women who used assisted reproductive technology (ART) or who were subfertile compared with women who conceived naturally. DESIGN: Retrospective cohort. SETTING: Deliveries among privately insured women aged ≥18 years between 2004 and 2017 from Massachusetts state vital records were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and hospital observational/inpatient stays. PATIENT(S): We compared patients with ART, medically assisted reproduction (MAR), and unassisted subfertile (USF) delivery with those with fertile delivery. INTERVENTION(S): NA. MAIN OUTCOME MEASURE(S): Postdelivery hospitalization information was derived from the International Classification of Diseases codes for discharges and combined by type. The relative risks and 95% confidence intervals (CIs) of hospitalization for up to the first 8 years postdelivery were modeled. RESULT(S): Among 492,515 deliveries, 5.6% used ART, 1.6% used MAR, and 1.8% were USF. Compared with fertile deliveries, deliveries that used ART or MAR or were USF were more likely to have hospital utilization (inpatient or observational stay) for any reason for up to 8 years of follow-up (USF, adjusted relative risk [aRR], 1.18 [95% CI, 1.12-1.25]; MAR, aRR, 1.20 [1.13-1.27]; and ART, aRR, 1.29 [1.25-1.34]). Assisted reproductive technology deliveries had an increased risk of hospitalization for conditions of the cardiovascular system (aRR, 1.31 [95% CI, 1.20-1.41]), overweight/obesity (aRR, 1.30 [1.17-1.44]), diabetes (aRR, 1.25 [1.05-1.49]), reproductive tract (aRR, 1.62 [1.47-1.79]), digestive tract (aRR, 1.39 [1.30-1.49]), thyroid (aRR, 2.02 [1.80-2.26]), respiratory system (aRR, 1.13 [1.03-1.24]), and cancer (aRR, 1.40 [1.18-1.65]) up to 8 years after delivery. Deliveries with MAR and subfertility had similar patterns of hospitalization as ART deliveries. CONCLUSION(S): Women who conceived through fertility treatment or experienced subfertility were at increased risk of subsequent hospitalization resulting from a variety of chronic and acute conditions.

The influence of the female reproductive tract and sperm features on the design of microfluidic sperm-sorting devices.

Although medical advancements have successfully helped a lot of couples with their infertility by assisted reproductive technologies (ART), sperm selection, a crucial stage in ART, has remained challenging. Therefore, we aimed to investigate novel sperm separation methods, specifically microfluidic systems, as they do sperm selection based on sperm and/or the female reproductive tract (FRT) features without inflicting any damage to the selected sperm during the process. In this review, after an exhaustive studying of FRT features, which can implement by microfluidics devices, the focus was centered on sperm selection and investigation devices. During this study, we tried not to only point to the deficiencies of these systems, but to put forth suggestions for their improvement as well.

Optimizing natural fertility: a committee opinion.

This committee opinion provides practitioners with suggestions for optimizing the likelihood of achieving pregnancy in couples or individuals attempting conception who have no evidence of infertility. This document replaces the document of the same name previously published in 2013 (Fertil Steril 2013;100:631-7).

Common practices among consistently high-performing in vitro fertilization programs in the United States: 10-year update.

OBJECTIVE: To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics. DESIGN: Cross-sectional questionnaire study of selected programs. SETTING: Academic and private fertility practices performing in vitro fertilization (IVF). PATIENT(S): Not applicable. INTERVENTION(S): A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years. MAIN OUTCOME MEASURE(S): Clinical and laboratory IVF practices. RESULT(S): Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators. CONCLUSION(S): Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients.

The altered immunological status of children conceived by assisted reproductive technology.

BACKGROUND: With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. METHODS: A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. RESULTS: Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = - 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). CONCLUSIONS: Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.

Singleton pregnancies conceived with infertility treatments and the risk of neonatal and infant mortality.

OBJECTIVES: To examine the risks of neonatal and infant mortality in relation to infertility treatment and to quantify the extent to which preterm delivery mediates this relationship. DESIGN: Cross-sectional study. SETTING: United States, 2015-2018. PATIENT(S): A total of 14,961,207 pregnancies resulting in a singleton live birth. INTERVENTION(S): Any infertility treatment, including assisted reproductive technology and fertility-enhancing drugs. MAIN OUTCOME MEASURE(S): Neonatal (<28 days) mortality. The effect measure, risk ratio (RR), and 95% confidence interval (CI) were derived from log-linear Poisson models. A causal mediation analysis of the relationship between infertility treatment and mortality associated with preterm delivery (<37 weeks) was performed. The effects of exposure misclassification and unmeasured confounding biases were assessed. RESULT(S): Any infertility treatment was documented in 1.3% (n = 198,986) of pregnancies. Infertility treatment was associated with a 51% increased risk of neonatal mortality (RR 1.51, 95% CI 1.39-1.64), with a slightly higher risk for early neonatal mortality (RR 1.57, 95% CI 1.43-1.73) than late neonatal mortality (RR 1.33, 95% CI 1.11-1.58). These risks were similar for pregnancies conceived through assisted reproductive technology and fertility-enhancing drugs. The mediation analysis showed that 72% (95% CI 59-85) of the total effect of infertility treatment on neonatal mortality was mediated through preterm delivery. In a sensitivity analysis, following corrections for exposure misclassification and unmeasured confounding biases, these risks were higher for early, but not for late, neonatal mortality. CONCLUSION(S): Pregnancies conceived with infertility treatment are associated with increased neonatal mortality, and this association is largely mediated through preterm delivery. However, given the substantial underreporting of infertility treatment, these associations must be cautiously interpreted.

Sperm DNA fragmentation index and cumulative live birth rate in a cohort of 2,713 couples undergoing assisted reproduction treatment.

OBJECTIVE: To study how the choice of the first assisted reproductive technology treatment type affects the cumulative live birth rate (CLBR) in couples with high sperm DNA fragmentation index (DFI). DESIGN: Longitudinal cohort study. SETTING: University-affiliated fertility clinic. PATIENT(S): A total of 2,713 infertile couples who underwent assisted reproductive technology treatment between 2007 and 2017 were included in the study. All in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments (up to three fresh treatments and all associated frozen-thawed embryo transfers) offered to the couples by the public health care system were included, in total 5,422 cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the CLBR. The secondary outcomes were the fertilization rate and the miscarriage rate. The IVF and ICSI groups were defined according to the method applied in the first treatment cycle. RESULT(S): In the IVF group, the CLBR values were higher for couples with normal DFI compared with those for couples with high DFI (≥20%) (48.1% vs. 41.6% for conservative CLBR estimate and 55.6% vs. 51.4% for optimal CLBR estimate after adjustment for female age, respectively). No DFI-dependent difference was seen in the ICSI group. CONCLUSION(S): Our results demonstrated that a high DFI predicts a statistically significantly lower CLBR if IVF and not ICSI is applied in the first cycle of assisted reproduction.

The impact of medical therapies and factors related to treatment procedures in women with rheumatoid arthritis and inflammatory bowel disease receiving assisted reproduction: a nationwide cohort study.

OBJECTIVE: To examine whether medications used to treat rheumatoid arthritis (RA)/chronic inflammatory bowel disease (IBD), or factors related to the assisted reproductive technology (ART) procedures, impact the success of ART. In women with RA/IBD, initial studies have shown a reduced chance of a live-born child after ART. DESIGN: Cohort study. SETTING: Nationwide Danish health registries. PATIENTS: All Danish women with a fresh embryo transfer from January 1, 2006, through 2018. The cohorts comprised 1,824 embryo transfers in women with RA/IBD and 97,191 embryo transfers in women without RA/IBD. INTERVENTIONS: Observational, noninterventional study. MAIN OUTCOME MEASURE: Live birth per fresh embryo transfer. RESULTS: The chance of a live birth in women with RA/IBD receiving ART, compared with other women receiving ART, had an adjusted odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.68-0.91). Prescribed corticosteroids before embryo transfer were positively associated with a live-born child (adjusted OR, 1.21; 95% CI, 1.12-1.31), while the use of antiinflammatory/immunosuppressive agents did not have significant importance. Intracytoplasmic sperm injection was associated with a reduced chance (adjusted OR, 0.94; 95% CI, 0.90-0.97). Type of hormone treatment protocol did not have significant importance, and transfer at the blastocyst stage was positively associated with a live-born child (adjusted OR, 1.54; 95% CI, 1.46-1.62). CONCLUSIONS: In women with RA and/or IBD, prescribed corticosteroid before embryo transfer and embryo transfer at the blastocyst stage were associated with successful ART. Intracytoplasmic sperm injection was associated with a slightly reduced chance. Antiinflammatory/immunosuppressive agents and type of hormone protocols did not have significant importance.

Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing FET. INTERVENTION(S): We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate. RESULT(S): Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs. CONCLUSION(S): Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET. PROSPERO NUMBER: CRD42019157071.

Innovations in infertility: a comprehensive analysis of the ClinicalTrials.gov database.

OBJECTIVE: To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion. DESIGN: Retrospective review of trials registered with ClinicalTrials.gov. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Descriptive statistics characterizing the attributes of the clinical trials including intervention type, topic, population, completion status, size, location, sponsor, and results. The effects of the sponsor and trial location on trial noncompletion were assessed via logistic regression. RESULT(S): In total, 505 trials initiated between 2010 and 2020 were included in our analysis. Drug interventions were the most commonly studied (45%); ovarian stimulation trials accounted for 27% of the studies. Live birth was tracked as an outcome by 20% of the studies; 3% of the trials included mental health outcomes. Few trials (15%) enrolled male participants. Only 11% of the trials reported results, and 4% of the trials reported the race or ethnicity of the participants. Most trials (82%) were conducted outside the United States. Overall, 18% of the trials were not completed, most often because of lack of accrual (47%). United States trials had over twice the odds of noncompletion in univariate analysis (odds ratio = 2.48, 95% confidence interval = [1.47, 4.17]); however, this relationship lost significance after adjusting for potential confounders (odds ratio = 0.95, 95% confidence interval = [0.42, 2.14]). Trial sponsorship was not associated with trial noncompletion. CONCLUSION(S): Infertility trials predominantly investigated drug interventions, particularly ovarian stimulation. Live birth was an infrequent outcome despite its relevance to patients. Clinical trials should aim to address the unmet needs in fertility care and be inclusive of underserved populations affected by infertility.

Celebrating 30 years of ART in Latin America; and the 2018 report.

RESEARCH QUESTION: What are the trends in patient characteristics, effectiveness and safety of assisted reproductive technology (ART) performed in Latin America over the past three decades, as well as the detailed outcomes of procedures initiated in 2018? DESIGN: Retrospective collection of multinational data including epidemiology and outcomes of ART performed between 1990 and 2018. RESULTS: Over these 30 years we report 955,117 initiated cycles, 191,191 deliveries and 238,045 live births. In 1990, 66.5% of women were ≤34 years and 8.7% ≥40 years; in 2018, 26.4% of women were ≤34 years and 32.0% were ≥40 years. In 1990, 60.4% of transfers included ≥3 embryos, falling to 13.5% in 2018, and single embryo transfer (SET) increased from 13.8% to 30.4% between 1990 and 2018. Delivery rate per fresh transfer increased from approximately 17% in the 1990s to 25% in 2018, with a meaningful drop in high-order multiples, from 5-9% in the 1990s to 0.4% in 2018. This drop is associated with increasing use of frozen embryo transfer (FET) (57% in 2018) compared with 10% in 2000. In 2018, delivery rate in FET was 28.3%, reaching 31.2% in freeze-all cycles; and the cumulative live birth rate (fresh + FET) was 41.9%. Elective SET also increased, from 0.9% in 2010 to 10% in 2018. The delivery rate in elective SET (31.7%) was only 5.4% lower than elective double embryo transfer (DET) (37.1%); however, multiple births increased from 2.1% to 25.5% twins and 0.4% triplets in elective DET. CONCLUSION: The Latin American Registry of Assisted Reproduction (RLA) celebrates 30 years of voluntary reporting from a total of nearly 200 centres in 15 countries. This South-South Cooperation network has proven to be an efficient and safe system for technological transfer and regional growth.

Artificial intelligence-the future is now.

The pros and cons of artificial intelligence in assisted reproductive technology are presented.

The effect of thyroid autoantibody on assisted reproduction technology outcome in euthyroid women: One center experience.

Thyroid dysfunction is an important factor to cause failure in assisted reproduction technology (ART) procedures. In this study, we recorded the serum level of thyroid autoantibody to fig. out its relationship with the ART outcome. The results showed that the serum concentrations of TSH had a statistically significant increase between the basal level and the levels at time of serum pregnancy test both in women with and without thyroid autoantibody (p= 0.002 and p=0.019, respectively). Additionally, the TSH level increased significantly in thyroid autoantibody-positive group than those in thyroid autoantibody-negative group during controlled ovarian hyper stimulation (COH) process(p = 0.006). The risk of preterm delivery was lower in thyroid autoantibody-negative group. In sum, the present study provided evidence of an association between thyroid autoantibody and preterm delivery in euthyroid women.

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

OBJECTIVE: To compare racial differences in male fertility history and treatment. DESIGN: Retrospective review of prospectively collected data. SETTING: North American reproductive urology centers. PATIENT(S): Males undergoing urologist fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and reproductive Andrology Research Consortium data. RESULT(S): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%). CONCLUSION(S): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.