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.

Racial and Ethnic Disparities in Access to and Outcomes of Infertility Treatment and Assisted Reproductive Technology in the United States.

Infertility disproportionately affects the minority, non-White populace, with Black women having twofold higher odds than White women. Despite higher infertility rates, minority racial and ethnic groups access and utilize fertility care less frequently. Even once care is accessed, racial and ethnic disparities exist in infertility treatment and ART outcomes. Preliminary studies indicate that Asian and American Indian women have lower intrauterine insemination pregnancy rates. Many robust studies indicate significant racial and ethnic disparities in rates of clinical pregnancy, live birth, pregnancy loss, and obstetrical complications following in vitro fertilization, with lower favorable outcomes in Black, Asian, and Hispanic women.

Impacts of the COVID-19 pandemic on Chinese assisted reproductive technology institutions and human sperm banks: reflections in the post-pandemic era.

OBJECTIVE: The COVID-19 pandemic has been the most serious public health emergency encountered in modern assisted reproductive technology (ART) development. In order to identify lessons learned, this study reviews the effect of the pandemic on ART institutions and human sperm banks in China, and summarizes the experiences and reflections of Chinese scholars post-pandemic era. METHODS: This review is based on multiple consensus statements on the COVID-19 pandemic issued by Chinese experts as well as current national regulations and principles in ART institutions and human sperm banks to document the current situation of ART services in China, describe the impact of the pandemic on these services, and offer Chinese reflections on worrying issues in the post-pandemic era. RESULTS: China reached one million ART cycles in 2016, and there are currently 540 ART medical institutions and 27 human sperm banks, with 540 licensed for AIH, 91 for AID, 415 for conventional IVF and ICSI and 85 for PGT. Of these, only 4 institutions carry out 10,000 cycles or more annually, and the proportion of institutions with less than 1,000 cycles has reached 66%, which means that a considerable number of ART institutions are still not saturated. As a consequence of the COVID-19 pandemic, 63.6% of ART providers and 95.5% of human sperm banks suspended operations. By the end of May 2020, China, as an early country affected by the pandemic achieved a national resumption rate of ART medical services of 99.2% and that of human sperm banks of 100.0%. Reports from the first and largest human sperm bank in China showed that qualification, semen concentration and sperm viability rates measured at primary screening have significantly decreased post-pandemic. Much like in other countries, Chinese experts developed a consensus on prevention and control measures during the pandemic. In principle, all ART activities should be suspended during acute phases of infection spread. Chinese scholars highlight that attention should be paid to young patients with fertility requirements during and after COVID-19, and emphasize the importance of fertility evaluation and clinical intervention. In addition, couples should be reminded that during ART treatment, disinfectants should not be used excessively to minimize risks of damaging the reproductive system, gametes and zygotes. At the same time, timely and reasonable guidance for tackling negative emotions from stress response is needed to provide reassurance and to avoid irrational fear and excessive stress. Seminal parameters should be re-examined 2 months after SARS-CoV-2 vaccination, and ART treatments recommenced if no abnormalities are detected. CONCLUSIONS: Given the growing frequency of outbreaks of global infectious diseases in recent years, ART institutions and human sperm banks should pay attention to improving their prevention and control capabilities. To a certain extent, decisions and measures adopted in China during COVID-19 pandemic are worthy of recognition and acceptance. Chinese scholars have discussed, proactively responded to and understand the key issues surrounding ART development during the pandemic with the aim of contributing to the substantial progress and healthy development of ART services in the world.

Model-based estimation of the health care expenditure and out-of-pocket payment for assisted reproductive technology: A retrospective linkage study using the Japanese national ART registry.

AIM: From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system. METHODS: We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model. RESULTS: We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%). CONCLUSIONS: Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations.

The challenges of selective fertility and carryover effects in within-sibship analyses: the effect of assisted reproductive technology on perinatal mortality as an example.

BACKGROUND: Within-sibship analyses show lower perinatal mortality after assisted reproductive technology (ART) compared with natural conception (NC), a finding that appears biologically unlikely. We investigated whether this may be attributed to bias from selective fertility and carryover effects. METHODS: Using data from national registries in Denmark (1994-2014), Finland (1990-2014) and Norway and Sweden (1988-2015), we studied 5 722 826 singleton pregnancies, including 119 900 ART-conceived and 37 590 exposure-discordant sibships. Perinatal mortality at the population level and within sibships was compared using multilevel logistic regression with random and fixed intercepts, respectively. We estimated selective fertility as the proportion of primiparous women with and without perinatal loss who had a second delivery, and carryover effects through bidirectional and crosswise associations. RESULTS: Population analysis showed higher perinatal mortality among ART conception compared with NC (odds ratio 1.21, 95% CI 1.13 to 1.30), whereas within-sibship analysis showed the opposite (OR 0.36, 95% CI 0.31 to 0.43). Primiparous women with perinatal loss were more likely to give birth again (selective fertility) and to use ART in this subsequent pregnancy (carryover effects), resulting in strong selection of double-discordant sibships with death of the naturally conceived and survival of the ART-conceived sibling. After controlling for conception method and outcome in the first pregnancy, ART was not consistently associated with perinatal mortality in the second pregnancy. CONCLUSIONS: Whereas population estimates may be biased by residual confounding, within-sibship estimates were biased by selective fertility and carryover effects. It remains unclear whether ART conception contributes to perinatal mortality.

Medically Assisted Reproduction Treatment Types and Birth Outcomes: A Between-Family and Within-Family Analysis.

OBJECTIVE: To compare risks of adverse birth outcomes among pregnancies conceived with and without medically assisted reproduction treatments. METHODS: Birth certificates were used to study birth outcomes of all neonates born in Utah from 2009 through 2017. Of the 469,919 deliveries, 52.8% (N=248,013) were included in the sample, with 5.2% of the neonates conceived through medically assisted reproduction. The outcome measures included birth weight, gestational age, low birth weight (LBW, less than 2,500 g), preterm birth (less than 37 weeks of gestation), and small for gestational age (SGA, birth weight less than the 10th percentile). Linear models were estimated for the continuous outcomes (birth weight, gestational age), and linear probability models were used for the binary outcomes (LBW, preterm birth, SGA). First, we compared the birth outcomes of neonates born after medically assisted reproduction and natural conception in the overall sample (between-family analyses), before and after adjustment for parental background and neonatal characteristics. Second, we employed family fixed effect models to investigate whether the birth outcomes of neonates conceived through medically assisted reproduction differed from those of their naturally conceived siblings (within-family comparisons). RESULTS: Neonates conceived through medically assisted reproduction weighed less, were born earlier, and were more likely to be LBW, preterm, and SGA than neonates conceived naturally. More invasive treatments (assisted reproductive technology [ART] and artificial insemination [AI] or intrauterine insemination) were associated with worse birth outcomes; for example, the proportion of LBW and preterm birth was 6.1% and 7.9% among neonates conceived naturally and 25.5% and 29.8% among neonates conceived through ART, respectively. After adjustments for various neonatal and parental characteristics, the differences in birth outcomes between neonates conceived through medically assisted reproduction and naturally were attenuated yet remained statistically significant; for example, neonates conceived through ART were at 3.2 percentage points higher risk for LBW (95% CI 2.4-4.1) and 4.8 percentage points higher risk for preterm birth (95% CI 3.9-5.7). Among siblings, the differences in the frequency of adverse outcomes between neonates conceived through medically assisted reproduction and neonates conceived naturally were small and statistically insignificant for all types of treatments. CONCLUSION: Medically assisted reproduction treatments are associated with adverse birth outcomes; however, those risks are unlikely to be associated with the infertility treatments itself.

A review of disparities in access to infertility care and treatment outcomes among Hispanic women.

Hispanic women have lower rates of use of infertility services than non-Hispanic White women. There are many barriers that impede access to infertility care including economic, geographic, cultural, and societal factors and there are disparities in treatment outcomes. Hispanic women are less likely to seek infertility care than non-Hispanic White women and even after infertility evaluation, Hispanic women are less likely to receive treatment for their infertility. Lower use of infertility treatments among Hispanic women is unlikely to be driven solely by economic factors. There is disappointingly little data on in-vitro fertilization treatment outcomes including the population of Hispanic women, and existing data has yielded conflicting results. Incomplete and variable reporting of race data across clinics raises the potential for misclassification bias and invalid study conclusions. Addressing disparities in access to reproductive medicine in the Hispanic population will required a multifaceted approach including expanded insurance coverage, improved education for both patients and providers, and additional research on barriers to care.

The Correlation Between Gross Domestic Product Per Capita and the Success Rate of Assisted Reproductive Technologies Worldwide.

OBJECTIVE: Although there has been increased utilization of assisted reproductive technologies (ART) in the world, there is no conclusive definition about the relationship between the success rate of ART and national wealth. METHODS: In this study, using the data from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART), we sought to determine whether there is a correlation between the success rate of ART (represented by pregnancy and delivery rates) and national wealth represented by the gross domestic product (GDP) per capita. Moreover, to further understand the effect of GDP per capita on ART effectiveness, we analyzed the association between ART success rate and GDP per capita in 50 US states. RESULTS: Our data showed that the number of ART treatment cycles increased as the GDP per capita increased. However, we found a negative correlation between ART success rates and GDP per capita in ICMART countries, although no correlation was seen in the US states. Using rough estimation, we derived that the success rate of ART was not related to GDP per capita in the ICMART countries with a GDP per capita greater than USD 13,000. CONCLUSIONS: In conclusion, for the first time, we showed that when the GDP per capita of an economic territory reaches (or exceeds) USD 13,000, ART pregnancy and delivery rates were not associated with GDP per capita, and ART success rates remained stable.

Protective placental inflammatory and oxidative stress responses are attenuated in the context of twin pregnancy and chorioamnionitis in assisted reproduction.

PURPOSE: Assisted reproduction technologies (ART) are associated with increased risks of pregnancy complications and obstetric interventions. Here, we aimed to determine if ART affects placental inflammation and oxidative stress as a mechanism for unfavorable pregnancy outcomes. METHODS: The levels of six cytokines (IFN-γ, IL-1ß, IL-6, IL-8, IL-10, TNFα) were measured using multiplex ELISA. The activity of four antioxidant enzymes (glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase, superoxide dismutase) and levels of two antioxidants (GSH, vitamin E) were measured using commercial/in-house assays. Markers were compared between ART and unassisted pregnancies, and then groups were stratified using ICD9/10 codes to determine differences in specific clinical contexts. RESULTS: In unassisted twin pregnancies, there was a trend of decreased cytokine levels (IL-1ß, IL-6, IL-8, TNFα, p < 0.05), but cytokines in ART twins were the same or higher. Additionally, GST and GPx activities were lower in unassisted twins, and vitamin E levels were higher in ART twins (p < 0.05). In pregnancies complicated by chorioamnionitis, there was a trend of increased cytokine levels in unassisted pregnancies (IL-1ß, IL-6, and IL-8, p < 0.05). No increase was observed in ART, and IFN-γ and TNFα were decreased (p < 0.05). Placental GST and GPx activities were higher in unassisted pregnancies with chorioamnionitis compared to ART (p < 0.05). CONCLUSION: Attenuation of protective placental inflammatory and oxidative stress responses may play a role in the underlying pathogenesis of negative birth outcomes in ART, expanding our understanding of adverse pregnancy outcomes when ART is used to conceive.

A comparative, observational study evaluating dosing characteristics and ovarian response using the recombinant human follicle-stimulating hormone pen injector with small-dose dial in assisted reproductive technologies treatment in Asia: IMPROVE study.

BACKGROUND: Ovarian stimulation during medically assisted reproduction treatment should be individualized to optimize outcomes and reduce complications. This study assessed whether use of the recombinant human follicle-stimulating hormone (r-hFSH) pen injector allowing small 12.5 IU dose increments resulted in lower r-hFSH dose per oocyte retrieved in a subgroup of patients at risk of OHSS, compared with r-hFSH injection devices allowing only 37.5 IU increments. METHODS: This multicenter, comparative, observational study evaluated patients from a prospective (study group) and historical (control group) cohort. The study group enrolled 1783 patients using the redesigned r-hFSH pen injector (GONAL-f®, Merck Healthcare KGaA, Darmstadt, Germany) from a prospective phase IV, non-interventional, open-label study, conducted in Korea, Vietnam, Indonesia, and China. The control group consisted of 1419 patients from a historical study using r-hFSH devices allowing 37.5 IU increments. In the study group, 397 patients were considered at risk of OHSS; this information was unavailable for the control group, so biomarkers and patient characteristics were used to match 123 patients from the study group and control group. Each center adhered to standard practice; starting dose and intra-cycle dose adjustments were allowed at any point. The primary endpoint, amount of r-hFSH (IU) administered per oocyte retrieved, was assessed in matched patients only. Additional outcomes and safety were assessed in the overall populations. RESULTS: Baseline characteristics were comparable between groups. Mean (SD) total dose of r-hFSH administered per oocyte retrieved in patients at risk of OHSS, was significantly lower in the study group compared with the control group (132.5 [85.2] vs. 332.7 [371.6] IU, P < 0.0001, n = 123). Implantation rate, clinical pregnancy rate, and live birth rates in the overall study and control groups were 30.0 vs. 20.6%, 50.3 vs. 40.7%, and 43.8 vs. 34.0%, respectively. OHSS incidence was significantly lower in the study group compared with the control group (27/1783 [1.5%] vs. 57/1419 [4.0%] patients, P < 0.0001). AEs were reported by 5.0% of patients in the study group. CONCLUSIONS: A significantly lower r-hFSH dose per oocyte retrieved and lower OHSS incidence were observed in patients using the redesigned injector compared with patients using other injection devices.

Are sperm parameters able to predict the success of assisted reproductive technology? A retrospective analysis of over 22,000 assisted reproductive technology cycles.

BACKGROUND: An explosive increase in couples attending assisted reproductive technology has been recently observed, despite an overall success rate of about 20%-30%. Considering the assisted reproductive technology-related economic and psycho-social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of assisted reproductive technology success, male parameters are largely underestimated so far. STUDY DESIGN: Retrospective, observational study. OBJECTIVES: To evaluate whether conventional semen parameters could predict assisted reproductive technology success. MATERIALS AND METHODS: All couples attending a single third-level fertility center from 1992 to 2020 were retrospectively enrolled, collecting all semen and assisted reproductive technology parameters of fresh cycles. Fertilization rate was the primary end-point, representing a parameter immediately dependent on male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to the World Health Organization manual editions used for semen analysis. RESULTS: Note that, 22,013 in vitro fertilization and intracytoplasmic sperm injection cycles were considered. Overall, fertilization rate was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective of the World Health Organization manual edition. In the in vitro fertilization setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted the fertilization rate (statistical accuracy = 71.1%). Sperm motilities also predicted pregnancy (p < 0.001) and live birth (p = 0.001) rates. In intracytoplasmic sperm injection cycles, sperm morphology predicted fertilization rate (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p < 0.001) and live birth (p < 0.001) rates and a cut-off of 5.5% was identified as a threshold to predict clinical pregnancy (area under the curve = 0.811, p < 0.001). DISCUSSION: Interestingly, sperm motility plays a role in predicting in vitro fertilization success, while sperm morphology is the relevant parameter in intracytoplasmic sperm injection cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples.

Dispensing of clomiphene citrate to treat infertility: medication supplied and population prevalence of assisted pregnancies and multiple births.

OBJECTIVE: To determine the proportion of pregnancies resulting in birth that were conceived with the use of clomiphene citrate (CC) and the frequency of multiple pregnancy. DESIGN: Whole-of-population cohort study, constructed through data linkage. Comprehensive Australian Government records of dispensed medications were linked to state Perinatal Registry records for all births of at least 20 weeks' gestation. SETTING: The state of South Australia. PATIENT(S): Women who maintained pregnancy for at least 20 weeks and gave birth between July 2003 and December 2015, a total of 150,713 women with 241,561 pregnancies. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Ongoing pregnancy occurring in proximity to CC, defined as dispensing from 90 days before to the end of a conception window derived from newborn date of birth and gestational age. RESULT(S): Linkage to dispensed prescription records was achieved for 97.9% of women. Women who conceived with CC tended to be older and socioeconomically advantaged and more likely than other women to have a history of miscarriage. Ongoing pregnancies associated with CC comprised 1.6% of the total; 5.7% were multiple births (mostly twins, 94.6%) compared with 1.5% in the remainder (98.5% twins). CONCLUSION(S): In South Australia, 1.6% of pregnancies (1 in 60) of at least 20 weeks' gestation were conceived proximal to CC dispensing. Of these, 5.7% were multiple pregnancies. This takes the proportion of women who achieved an ongoing pregnancy with medical assistance from 4.4%, based on reports from assisted reproductive technology clinics, to 6% in total.

Long-term reproductive outcomes in patients with unexplained infertility: follow-up of the Fast Track and Standard Treatment Trial participants.

OBJECTIVE: To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility. DESIGN: Telephone survey, administered between March 2019 and February 2020. SETTING: Large urban university-affiliated fertility center. PATIENT(S): Couples who enrolled in the Fast Track and Standard Treatment Trial (FASTT). INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Number of live births, methods of conception, adoption, and satisfaction regarding family size. RESULT(S): Of the 503 couples enrolled in FASTT, 311 (61.8%) were contacted and 286 (56.9%) consented to participate. The mean age and follicle-stimulating hormone level at the time of enrollment in FASTT were 33.1 ± 3.2 years and 6.8 ± 2.2 mIU/mL, respectively, for those who participated in this study. The mean age at follow-up was 49.5 ± 3.4 years. Of the 286 women, 194 (67.8%) had a live birth during the trial and 225 (78.7%) continued to try to conceive after FASTT. Of those who tried to conceive without treatment, 101 of 157 (64.3%) had a successful live birth, whereas 12 (5.3%) women had a live birth via intrauterine insemination and 82 (36.4%) via autologous oocyte in vitro fertilization. Overall, 182 (80.9%) women achieved a live birth after FASTT. CONCLUSION(S): The majority of couples were able to achieve a live birth after FASTT. Only 19 (6.6%) never achieved a live birth during their reproductive years. Moving to treatment sooner allows the opportunity to achieve >1 live birth, which is associated with increased satisfaction regarding family size. This further supports access to care and insurance coverage for infertility treatment.

Prevalence and performance of private equity-affiliated fertility practices in the United States.

OBJECTIVE: To quantify the proportion of annual assisted reproductive technology (ART) cycles performed at private equity-affiliated fertility practices and to test for differences in services and success rates between private equity-affiliated and nonaffiliated practices. DESIGN: Cross-sectional analysis of national data set. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The primary outcome measures were the volume of ART cycles performed, the percentage of retrievals resulting in live births, and the percentage of transfers resulting in live births. The secondary outcomes included the median income of the practice location, the use of preimplantation genetic testing, the clinical service availability, and the patient reasons for seeking treatment. RESULT(S): Of the practices listed on the Centers for Disease Control's 2018 Fertility Clinic Success Rates Report, 14.7% had a private equity affiliation. Of the 305,883 ART cycles performed in 2018, 29.3% (89,535) occurred at private equity-affiliated practices. Patients at private equity-affiliated practices were 6.75% (95% confidence interval [CI], -10.15%, -3.36%) less likely to initiate a cycle due to male factor infertility, and 10.60% (95% CI, 3.49, 17.76) more likely to use preimplantation genetic testing before embryo transfer. No statistically significant differences were found in success rates among women aged <35 years. The average median household income (standard error) in zip codes with private equity-affiliated practices compared with nonaffiliated practices was $83,610 ($35,990) and $72,161 ($32,314), respectively. CONCLUSION(S): A major portion of fertility practices in the United States are private equity-affiliated, and these practices perform an even greater portion of ART cycles in the United States each year. Fertility appears to be the medical specialty with the greatest market share owned by private equity. Our findings corroborate preliminary research, which forecasts the increasing involvement and consolidation by private equity in fertility. Future research should continue monitoring for differences in outcomes, financing, case mix, service use, and accessibility.

Is It Possible to Expand Oocyte Donors by Decreasing Number of Oocytes for Own Use? Insights From a Large Single-Center Study.

Background: Currently, in China, only women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles can donate oocytes to others, but at least 15 oocytes must be kept for their own treatment. Thus, the aim of this study was to determine whether oocyte donation compromises the cumulative live birth rate (CLBR) of donors and whether it is possible to expand oocyte donors' crowd. Methods: This was a retrospective cohort study from August 2015 to July 2017 including a total of 2,144 patients, in which 830 IVF-embryo transfer (IVF-ET) patients were eligible for oocyte donation and 1,314 patients met all other oocyte donation criteria but had fewer oocytes retrieved (10-17 oocytes). All 830 patients were advised to donate approximately three to five oocytes to others and were eventually divided into two groups: the oocyte donation group (those who donated) and the control group (those who declined). The basic patient parameters and CLBR, as well as the number of supernumerary embryos after achieving live birth, were compared. These two factors were also compared in all patients (2,144) with oocyte ≥10. Results: In 830 IVF-ET patients who were eligible for oocyte donation, only the oocyte number was significantly different between two groups, and the donation group had more than the control group (25.49 ± 5.76 vs. 22.88 ± 5.11, respectively; p = 0.09). No significant differences were found between the two groups in other factors. The results indicate that the live birth rate in the donation group was higher than that in the control group (81.31% vs. 82.95%, p = 0.371), without significance. In addition, CLBR can still reach as high as 73% when the oocyte number for own use was 10. Supernumerary embryos also increased as the oocyte number increased in all patients (oocyte ≥10). Conclusions: Currently, oocyte donation did not compromise CLBR, and oocyte donation can decrease the waste of embryos. In addition, in patients with 10 oocytes retrieved, the CLBR was still good (73%). Thus, it is possible to expand oocyte donors if the number of oocyte kept for own use was decreased from 15 to 10 after enough communication with patients.

Differences in ICSI utilization rates among states with insurance mandates for ART coverage.

BACKGROUND: Assisted reproductive technology (ART) insurance mandates promote more selective utilization of ART clinic resources including intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ICSI utilization differs by state insurance mandates for ART coverage and assess if such a difference is associated with male factor, preimplantation genetic testing (PGT), and/or live birth rates. METHODS: In this retrospective analysis of the Centers for Disease Control (CDC) data from 2018, ART clinics in ART-mandated states (n = 8, AR, CT, HI, IL, MD, MA, NJ, RI) were compared individually to one another and with non-mandated states in aggregate (n = 42) for use of ICSI, male factor, PGT, and live birth rates. ANOVA was used to evaluate differences between ART-mandated states and non-mandated states. Individual ART-mandated states were compared using Welch t-tests. Statistical significance was determined by Bonferroni Correction. RESULTS: There were significant differences in ICSI rates (%, mean ± SD) between MA (53.3 ± 21.3) and HI (90.7 ± 19.6), p = 0.028; IL (86.5 ± 18.7) and MA, p = 0.002; IL and MD (57.2 ± 30.8), p = 0.039; IL and NJ (62.0 ± 26.8), p = 0.007; between non-mandated states in aggregate (79.9 ± 19.9) and MA, p = 0.006, and NJ (62.0 ± 26.8), p = 0.02. Male factor rates of HI (65.8 ± 16.0) were significantly greater compared to CT (18.8 ± 8.7), IL (26.0 ± 11.9), MA (26.9 ± 6.6), MD (29.3 ± 9.9), NJ (30.6 ± 17.9), and non-mandated states in aggregate (29.7 ± 13.7), all p < 0.0001. No significant differences were reported for use of PGT and/or live birth rates across all age groups regardless of mandate status. CONCLUSIONS: ICSI use varied significantly among ART-mandated states while demonstrating no differences in live birth rates. These data suggest that the prevalence of male factor and the presence of a state insurance mandate are not the only factors influencing ICSI use. It is suggested that other non-clinical factors may impact the rate of ICSI utilization in a given state.

Assessment of Cardiovascular Health of Children Ages 6 to 10 Years Conceived by Assisted Reproductive Technology.

Importance: Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies. Objective: To assess the cardiovascular health of children conceived by ART. Design, Setting, and Participants: This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child's birth (2 years older or younger). Data were analyzed from March 2019 through December 2019. Exposures: Conception by ART. Main Outcomes and Measures: Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more. Results: Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P < .001; mean [SD] diastolic blood pressure, 67.2 [5.6] mm Hg vs 62.2 [6.3] mm Hg ; adjusted P < .001), left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 64.61% [3.20%] vs 66.70% [3.89%]; adjusted P < .001), and diastolic dysfunction (mean [SD] early/late mitral/tricuspid diastolic velocities ratio, 1.66 [0.28] vs 2.21 [0.36]; adjusted P < .001). They also had statistically significantly increased parameters of left ventricular structure, including mean (SD) left ventricular mass index (31.97 [5.04] g/m2.7 vs 28.28 [3.54] g/m2.7; adjusted P < .001) and RWT (3.30 [0.41] mm vs 2.98 [0.14] mm; adjusted P < .001). Additionally, children conceived by ART had statistically significantly increased prevalence of left ventricular hypertrophy (9 children [2.4%] vs 2 children [0.5%]; P = .03), high RWT (61 children [16.0%] vs 0 children; P < .001), and left ventricle remodeling patterns, including concentric remodeling (60 children [15.7%] vs 0 children), eccentric hypertrophy (8 children [2.1%] vs 2 children [0.5%]), and concentric hypertrophy (1 child [0.3%] vs 0 children) (P for left ventricle remodeling < .001). Conclusions and Relevance: This study found that children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived. These findings suggest that further studies are needed to investigate the potential mechanisms and long-term outcomes associated with these differences.

Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study.

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

Has oncofertility information for male patients improved? Objective assessment of internet-based fertility preservation resources at NCI cancer centers from 2015 to 2020.

PURPOSE: Fertility preservation is a critical patient counseling component following cancer diagnosis. The aim of this study was to compare change and quality of fertility preservation information available to patients on the websites of National Cancer Institute (NCI)-designated cancer centers over 5 years (2015 to 2020) for both women and men. METHODS: All NCI-designated cancer center websites were queried for information on oncofertility in 2020 publicly available to patients using the methodology and rubric previously employed in 2015. Data was evaluated based on each center's city, county, and state by demographic data obtained from the US Census. Additionally, the yearly number of in vitro fertilization (IVF) cycles performed in the city, county, and state of each NCICC was included using websites of clinics reporting data to the Society for Assisted Reproductive Technology. RESULTS: Significantly NCICCs have a standalone pages for fertility preservation in 2020 compared with 2015 (p = 0.004). There is a statistically significant association between discussion of male fertility and the number of fertility centers in the county and state of the NCICC (p = 0.04 and p = 0.001). NCICCs in counties in the highest quartile of per capita income were significantly more likely to address male fertility (p = 0.03). CONCLUSIONS: Oncofertility information on NCICC websites has improved between 2015 and 2020. The impact of cancer treatment on male fertility, while improved, is still limited, particularly in counties with lower per capita income.

Effects of the early phase of the COVID-19 pandemic on natural and ART-mediated birth rates in Lombardy Region, Northern Italy.

RESEARCH QUESTION: What effects did the early phase of the COVID-19 pandemic have on natural and assisted reproductive technology (ART)-mediated birth rates? DESIGN: Regional registries were consulted with permission from the Health Authorities of Lombardy Region, Northern Italy, an area particularly affected by the early phase of the epidemic. Deliveries occurring in the area between 1 January 2019 and 31 December 2020 from women beneficiaries of the National Health System and resident in Lombardy were identified. Comparisons mainly focused on December 2020, when women who conceived after 8 March (the start of the stringent lockdown imposed by the authorities) were expected to deliver. RESULTS: When comparing the periods January to November in 2019 and 2020, a 5.1% reduction of monthly general birth rate (from 5732 in 2019 to 5438 in 2020) was observed. The contribution of ART births was similar in 2019 and 2020, being 4.4% and 4.5%, respectively. In December 2020, a notable drop in natural (-17.8%), ART-mediated (-86.6%) and overall (-21.0%) births was observed compared with December 2019. After adjusting for the expected 5.1% reduction, the inferred effect of the COVID-19 crisis corresponded to a 16.7% reduction in birth rate, of which 76% was related to natural (707 births) and 24% to ART (218 births) conceptions. CONCLUSIONS: This is the first study providing population-based evidence on the effects of COVID-19 and its related stringent restrictions on birth rates. The birth rate was dramatically reduced following the critical period, and the closure of ART centres played only a marginal role (24%) in the overall detrimental effect.