Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program.

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy. Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021. Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF. Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021). Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%). Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

Is the use of IVF add-on treatments driven by patients or clinics? Findings from a UK patient survey.

There are conflicting narratives over what drives demand for add-ons. We undertook an online survey of IVF patients to determine whether patients perceive that use of IVF add-ons is driven by patients or practitioners. People who underwent IVF in the UK in the previous five years were recruited via social media Survey questions focussed on the roles of clinician offer and patient request, including who first suggested use of add-ons in IVF consultations, where patients first heard about them, and which information sources they trusted. From a total of 261 responses, 224 met the inclusion criteria. Overall, 67% of respondents had used one or more IVF add-ons, most commonly: time-lapse imaging (27%), EmbryoGlue (27%), and endometrial scratching (26%). Overall, 81% of the add-ons used were offered to participants by clinicians (compared to 19% requested by themselves). Half (54%) reported being offered add-ons during consultations, compared to 24% who initiated discussion about add-ons. Higher proportions of private patients reported being offered (90%), requesting (47%) and using (74%) add-ons than those with NHS funding (74%, 29%, 52%, respectively). The main limitations of this study are the small sample size, recruitment via a convenience sample, and the self-reported data capture which is subject to recall bias.

Outcomes between non-IVF and IVF treatment after laparoscopic conservative surgery of advanced endometriosis with Endometriosis Fertility Index score >3.

Surgical excision of advanced endometriosis has been demonstrated to improve women's pain symptoms and quality of life in women in randomized placebo-controlled trials, but there is no strong evidence regarding the live birth rate. The revised American Fertility Society (r-AFS) classification for endometriosis has a limited predictive ability for fertility outcomes after surgery; therefore, EFI scoring has been advised for predicting conception after endometriosis surgery. No randomized controlled trials have investigated fertility outcomes in patients with advanced endometriosis after surgery. This study aimed to determine the outcomes of in vitro fertilization (IVF) or non-IVF treatments after conservative surgery for advanced endometriosis in patients with good prognosis Endometriosis Fertility Index (EFI) scores (>3). This prospective cohort study was conducted between April 2014 and April 2019 at a tertiary research hospital. In total, 113 women with suspected preoperative advanced endometriosis were enrolled in this study. A total of 90 women with advanced endometriosis underwent laparoscopic surgery. Fourteen patients with EFI score of ≤3 and 3 of them who had bilateral tubal occlusion were also excluded. Seventy-three women were included in this study. The remaining 30 women in the non-IVF group and 32 women in the IVF group were analyzed. The main outcome measures were cumulative pregnancy rates and live birth rates in both groups. Women who underwent IVF treatment were older than women (30 ±â€…3.41) who had non-IVF treatment (26.5 ±â€…3.07) after laparoscopic surgery (P < .001). The remaining baseline characteristics of the patients in both groups were similar. Clinical pregnancy, abortion, and live birth rates were similar in both the groups after 36 months of follow-up. This study demonstrated that cumulative pregnancy and live birth rates were similar to those of non-IVF or IVF treatments after conservative surgery for advanced endometriosis, if patients had good prognosis EFI scores. Furthermore, non-IVF treatments resulted in nearly the same clinical pregnancy results as IVF treatment within 1 year after surgery.

Effect of previous wedge resection for interstitial pregnancy on pregnancy and neonatal outcomes following frozen-thawed embryo transfer (FET) cycles of IVF/ICSI: a retrospective study.

OBJECTIVE: The present study aimed to evaluate pregnancy and neonatal outcomes in women, with a previous history of wedge resection for interstitial pregnancy, in frozen-thawed embryo transfer (FET) cycles of IVF/ICSI. METHODS: The present study involved a retrospective case-control assessment of 75 cases and 375 control subjects over 6 years in a single center. To compare pregnancy and neonatal outcomes between cases, treated using wedge resection, and controls without any previous history of ectopic pregnancy, propensity score matching (1:5) was utilized. The study also compared subgroups in the case group. RESULTS: Women with previous wedge resection exhibited higher rates of ectopic pregnancy and uterine rupture rate as compared to control subjects (9.1% vs 1.3%, P = 0.025 and 4.5% vs 0%, P = 0.035, respectively). No statistically significant differences were recorded between the two cohorts with regard to clinical pregnancy rate, live birth rate, and neonatal outcomes. For pregnancy type subgroup analysis, Z-score and rates of large for gestational age were recorded to be significantly lower in twin pregnancy subgroup when compared with singleton pregnancy subgroup (0.10 (- 0.59, 0.25) vs 0.50 (- 0.97, 1.39), P = 0.005; 4.5% vs 26.1%, P = 0.047, respectively). CONCLUSION: The results of the present study indicated that previous wedge resection correlated to a higher risk of ectopic pregnancy and uterine rupture. However, it might not be related to an increased risk of adverse neonatal outcomes. The study recommended cesarean section in these patients. Further studies are required to verify the validity of current recommendations.

Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles. METHODS: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study. RESULTS: Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02-1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05). CONCLUSION: The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, Chictr-TRC-14004494.

Sex ratio imbalance following blastocyst transfer is associated with ICSI but not with IVF: an analysis of 14,892 single embryo transfer cycles.

PURPOSE: Assisted reproductive technology (ART) has an impact on secondary sex ratio (SSR), which is seemed to be elevated after blastocyst transfer (BT) but decreased following ICSI procedure. We aim to assess whether the higher SSR associated with BT could be influenced by fertilization method used. METHODS: All consecutive IVF/ICSI cycles (fresh and frozen) involving single embryo transfer (SET) resulting in a live birth between 2015 and 2019 were retrospective analyzed. Logistic regression was used to model the effect on the SSR of maternal and specific ART characteristics. RESULTS: Six thousand nine hundred twenty-two women were included with the crude SSR of 54.8%. The impact of BT on SSR is influenced by the fertilization method used. After adjustment for potential confounders, the SSR in the ICSI BT group was significantly higher when compared to ICSI cleavage-stage embryo SET (aOR 1.24; 95% CI 1.10-1.40, P < 0.001). However, this effect was not detected among SBT with IVF treatment (aOR 1.04; 95% CI 0.97-1.12, P = 0.260). Assessing blastocyst morphological parameters, high trophectoderm quality was significantly associated with elevated SSR (aOR 1.76, 95% CI 1.34-2.31 [A vs. C], and aOR 1.28, 95% CI 1.14-1.44 [B vs. C]). No significant difference was shown in expansion, inner cell mass, or days of blastocyst formation between male and female blastocysts. CONCLUSIONS: The impact of BT on SSR could be influenced by the fertilization method used. The higher SSR was observed after BT with ICSI procedures but not with IVF. Interpretation of the findings is limited by the potential for selection and confounding bias.

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.

Analysis and quantification of female and male contributions to the first stages of embryonic kinetics: study from a time-lapse system.

PURPOSE: The few studies that examined the effect of male and/or female features on early embryo development, notably using the time-lapse system (TL), reported conflicting results. This can be explained by the small number of studies using an adapted model. METHODS: We used two original designs to study the female and male effects on embryo development: (1) based on embryos from donor oocytes (TL-DO), and (2) from donor sperm (TL-DS). Firstly, we analyzed the female and male similarities using an ad hoc intraclass correlation coefficient (ICC), then we completed the analysis with a multivariable model to assess the association between both male and female factors, and early embryo kinetics. A total of 572 mature oocytes (TL-DO: 293; TL-DS: 279), fertilized by intracytoplasmic sperm injection (ICSI) and incubated in a TL (Embryoscope®) were included from March 2013 to April 2019; 429 fertilized oocytes (TL-DO: 212; TL-DS: 217) were assessed. The timings of the first 48 h have been analyzed. RESULTS: The similarities in the timings thought to be related to the female component were significant: (ICC in both DO-DS designs respectively: tPB2: 9-18%; tPNa: 16-21%; tPNf: 40-26%; t2: 38-24%; t3: 15-20%; t4: 21-32%). Comparatively, those related to male were lower. Surprisingly after multivariable analyses, no intrinsic female factors were clearly identified. However, in TL-DO design, oligozoospermia was associated with a tendency to longer timings, notably for tPB2 (p = 0.026). CONCLUSION: This study quantifies the role of the oocyte in the first embryo cleavages, but without identified specific female factors. However, it also highlights that sperm may have an early embryonic effect.

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 association of in vitro fertilization/intracytoplasmic sperm injection results with anxiety levels and stress biomarkers: An observational, case-control study✰.

INTRODUCTION: Anxiety has been considered to exert a negative influence on fecundity. However, it remains unclear whether it is a cause or a consequence and whether it is associated with the treatment outcome. This observational case control study evaluated the levels of state anxiety and various stress biomarkers and assessed their association with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. MATERIALS AND METHODS: We allocated 109 infertile nulliparous women aged 25-45 years in their first IVF/ICSI fresh treatment cycle into two groups according to the final outcome: group A (PTP = pregnancy-test positive, n = 49) and group B (PTN = pregnancy-test negative, n = 60). State anxiety levels were measured with the Spielberger Trait Anxiety Inventory (STAI) questionnaire (Marteau and Bekker modification) on the days of oocyte retrieval (OR) and embryo transfer (ET). Serum stress biomarkers (cortisol, adrenaline, noradrenaline, α-amylase, and prolactin) were measured at the same time points. Blood samples were collected at 9 am. RESULTS: Most women in both groups showed comparable mild-to-moderate degrees of state anxiety on the days of OR and ET (p = 0.183 and p = 0.760, respectively). The stress biomarker measurements did not differ between the two groups, except for noradrenaline that was higher in group B (p = 0.015) and associated with significant cardiovascular changes. DISCUSSION: Women in both groups showed comparable levels of state anxiety, which were unlikely to influence the chance of pregnancy. Noradrenaline levels were higher in the non-pregnant group, with significant cardiovascular changes. Other stress biomarkers did not reflect the different treatment outcomes between the groups.

Impact of body mass index (BMI) on the success rate of fresh embryo transfer in women undergoing first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.

OBJECTIVE: To investigate the impact of body mass index (BMI) on the success rate and prenatal outcomes of fresh embryo transfer in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. METHODS: It is a post-hoc analysis of a prospective observational cohort study. 2569 Chinese women were grouped in quintiles of BMI and according to the official Chinese classification of body weight. IVF/ICSI and pregnancy outcomes were compared between groups. RESULTS: BMI was not associated with IVF/ICSI pregnancy outcomes including hCG positive rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, ongoing pregnancy rate, early miscarriage rate, and live birth rate. However, it was negatively related to some pregnancy complications such as gestational diabetes mellitus (GDM) and hypertension. Additionally, the proportion of Cesarean-section was increased with BMI. As for prenatal outcomes, the current results showed no statistical difference in the number of male and female newborn, the proportion of low live birth weight (<2500 g), macrosomia (≥4000 g) (both in all live birth and full-term live birth), and premature delivery (<37 weeks). CONCLUSIONS: The current study showed that BMI was not associated with embryo transfer outcomes after fresh embryo transfer in women undergoing their first IVF/ICSI treatment, whereas BMI was associated with GDM and gestational hypertension.

Decreased DNA Repair Ability: A Mechanism for Low Early Embryonic Development Potential of Oocytes From Overweight Patients After Fertilization in IVF Cycles.

Background: Whether female BMI impacts the DNA repair ability in the oocytes after fertilization has not been investigated. The aim of this study is to assess the early embryo quality and reproductive outcomes of oocytes from overweight women when fertilized with sperm with varying degrees of DNA fragmentation. Methods: A total number of 1,612 patients undergoing fresh autologous in vitro fertilization (IVF) cycles was included. These patients were divided into two groups according to maternal body mass index (BMI): normal weight group (18.5-24.9 kg/m2; n=1187; 73.64%) and overweight group (≥25 kg/m2; n=425; 26.36%). Each group was then subdivided into two groups by sperm DNA fragmentation index (DFI): low fragmentation group (<20% DFI, LF) and high fragmentation group (≥20% DFI, HF). Laboratory and clinical outcomes were compared between subgroups. Results: For the normal-weight group, there was no statistical significance in embryo quality and reproductive outcomes between the LF and HF groups. But in the overweight group, significantly lower fertilization rate (LF: 64%; HF: 59%; p=0.011), blastocyst development rate (LF: 57%; HF: 44%; p=0.001), as well as high-quality blastocyst rate (LF: 32%; HF: 22%; p=0.034) were found in the HF group, despite the similar pregnancy rates (LF: 56%; HF: 60%; p=0.630). Conclusions: Decreased DNA repair activity in oocytes may be a possible mechanism for the low early development potential of embryos from overweight patients in in vitro fertilization cycles.

A Premature Rise of Luteinizing Hormone Is Associated With a Reduced Cumulative Live Birth Rate in Patients ≥37 Years Old Undergoing GnRH Antagonist In Vitro Fertilization Cycles.

This is a retrospective cohort study included 1021 patients underwent a flexible GnRH antagonist IVF protocol from January 2017 to December 2017 to explore the effect of a premature rise in luteinizing hormone (LH) level on the cumulative live birth rate. All patients included received the first ovarian stimulation and finished a follow-up for 3 years. A premature rise in LH was defined as an LH level >10 IU/L or >50% rise from baseline during ovarian stimulation. The cumulative live birth rate was calculated as the number of women who achieved a live birth divided by the total number of women who had either delivered a baby or had used up all their embryos received from the first stimulated cycle. In the advanced patients (≥37 years), the cumulative live birth rate was reduced in patients with a premature rise of LH (ß: 0.20; 95% CI: 0.05-0.88; p=0.03), compared to patients (≥37 years) without the premature LH rise. The incidence of premature LH rise is associated with decreased rates of cumulative live birth rate in patients of advanced age (≥37 years) and aggravated the reduced potential of embryos produced by the advanced age, not the number of embryos.

Association of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles: a retrospective cohort study.

BACKGROUND: Parental body mass index (BMI) is associated with pregnancy outcomes. But the effect of parental prepregnancy BMI on offspring conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially the birth defect, remains to be determined. This study aimed to investigate the associations of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles. METHODS: We conducted a retrospective cohort study including 5741 couples in their first fresh IVF/ICSI cycles admitted to Women's Hospital, School of Medicine, Zhejiang University from January 2013 to July 2016. The primary outcome was birth defects, which was classified according to the International Classification of Diseases, 10th Revision. Secondary outcomes included preterm delivery rate, infant gender, birth weight, small-for-gestational age (SGA) and large-for-gestational age (LGA). Multilevel regression analyses were used to assess the associations of parental prepregnancy BMI with neonatal outcomes and birth defect. RESULTS: In singletons, couples with prepregnancy BMI ≥25 kg/m2 had higher odds of LGA than those with BMI < 25 kg/m2. The birth defect rate was significantly higher when paternal prepregnancy BMI ≥25 kg/m2 in IVF cycles (aOR 1.82, 95% CI 1.06-3.10) and maternal BMI ≥25 kg/m2 in ICSI cycles (aOR 4.89, 95% CI 1.45-16.53). For subcategories of birth defects, only the odds of congenital malformations of musculoskeletal system was significantly increased in IVF offspring with paternal BMI ≥25 kg/m2 (aOR 4.55, 95% CI 1.32-15.71). For twins, there was no significant difference among four groups, except for the lower birth weight of IVF female infants. CONCLUSIONS: Parental prepregnancy BMI ≥25 kg/m2 is associated with higher incidence of LGA in IVF/ICSI singletons. Paternal prepregnancy BMI ≥25 kg/m2 was likely to have higher risk of birth defect in IVF offspring than those with BMI < 25 kg/m2, particularly in the musculoskeletal system. It is essential for overweight or obesity couples to lose weight before IVF/ICSI treatments.

GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve.

Objective: To evaluate the efficiency and validity of cessation of cetrorelix on trigger day during gonadotropin releasing hormone antagonist (GnRH-ant)-controlled ovarian stimulation of in vitro fertilization (IVF) cycles. Methods: In this retrospective study, a total of 1271 patients undergoing initial IVF cycles following the GnRH-ant protocol were enrolled; 832 patients received cetrorelix on trigger day (Group A) and 439 patients ceased cetrorelix on trigger day (Group B). We compared demographic characteristics, embryological and clinical outcomes between the two groups. A Poisson regression model was used to identify factors that significantly affected embryological outcomes. Patients were further divided into subgroups according to anti-Mullerian hormone (AMH) and age, to assess associations between ceasing cetrorelix on trigger day and embryological outcomes. Results: There was a significant improvement on embryological outcomes in patients who ceased cetrorelix on trigger day, and there were no significant differences in clinical outcomes or preovulation rates between the two groups. Furthermore, for patients with 1.1 ≤ AMH ≤ 4.7 ng/ml, all embryological outcomes were significantly higher in Group B compared with Group A. For patients with AMH > 4.7 ng/ml, the number of oocytes retrieved, fertilization rate (2PN) of IVF cycles and proportion of day 3 good quality embryos were all significantly higher in Group B. For patients with age < 35 years, all the embryological outcomes, besides the number of available embryos, were significantly higher in Group B than in Group A. There were no differences in embryological outcomes between the two groups when patients were stratified based on age > 35 years or AMH < 1.1 ng/ml. Conclusion: GnRH-ant protocol with cessation of cetrorelix on trigger day improved embryological outcomes for young patients or patients with sufficient ovarian reserve, and was effective at preventing preovulation.

Analysis of IVF live birth outcomes with and without preimplantation genetic testing for aneuploidy (PGT-A): UK Human Fertilisation and Embryology Authority data collection 2016-2018.

PURPOSE: To examine the live birth and other outcomes reported with and without preimplantation genetic testing for aneuploidy (PGT-A) in the United Kingdom (UK) Human Embryology and Fertilization Authority (HFEA) data collection. METHODS: A retrospective cohort analysis was conducted following freedom of information (FoI) requests to the HFEA for the PGT-A and non-PGT-A cycle outcomes for 2016-2018. Statistical analysis of differences between PGT-A and non-PGT-A cycles was performed. Other than grouping by maternal age, no further confounders were controlled for; fresh and frozen transfers were included. RESULTS: Outcomes collected between 2016 and 2018 included total number of cycles, cycles with no embryo transfer, total number of embryos transferred, live birth rate (LBR) per embryo transferred and live birth rate per treatment cycle. Data was available for 2464 PGT-A out of a total 190,010 cycles. LBR per embryo transferred and LBR per treatment cycle (including cycles with no transfer) were significantly higher for all PGT-A vs non-PGT-A age groups (including under 35), with nearly all single embryo transfers (SET) after PGT-A (significantly more in non-PGT-A) and a reduced number of transfers per live birth particularly for cycles with maternal age over 40 years. CONCLUSION: The retrospective study provides strong evidence for the benefits of PGT-A in terms of live births per embryo transferred and per cycle started but is limited in terms of matching PGT-A and non-PGT-A cohorts (e.g. in future studies, other confounders could be controlled for). This data challenges the HFEA "red traffic light" guidance that states there is "no evidence that PGT-A is effective or safe" and hence suggests the statement be revisited in the light of this and other new data.

Impact of human papillomavirus infection on semen parameters and reproductive outcomes.

BACKGROUND: Human papillomavirus (HPV) has been shown to adversely affect human reproduction. We aimed to evaluate the prevalence of human papillomavirus (HPV) infection in men and its correlation with semen parameters and reproductive outcomes. METHODS: Semen samples and penile swabs were collected from potential sperm donors (SD, n = 97) and male partners of infertile couples (IM, n = 328). The presence of HPV DNA in semen samples and penile swabs was analyzed. Associations between hrHPV positive status and fertility outcomes as well as socio-behavioral and health characteristics were evaluated using the R software package. RESULTS: High-risk HPV (hrHPV) genotypes were detected in 28.9% of SD and 35.1% of IM (P = 0.312). Penile swabs were more frequently positive for hrHPV genotypes than semen samples in both IM (32.3% vs. 11.9%, P < 0.001) and SD (26.8% vs. 6.2%, P = 0.006). Men with hrHPV positive semen samples had lower semen volume (median volume 2.5 ml vs. 3 ml, P = 0.009), sperm concentration (median concentration 16 × 106/ml vs. 31 × 106/ml, P = 0.009) and total sperm count (median count 46 × 106 vs. 82 × 106, P = 0.009) than men with hrHPV negative samples. No association was identified between penile hrHPV status and semen parameters. CONCLUSIONS: Our findings indicate that penile HPV infection is common in both potential sperm donors and men from infertile couples. Although HPV positivity is higher in penile swabs, only HPV infection in semen samples affects sperm parameters. However, there was no association between hrHPV positivity in semen and fertility outcomes including abortion rate.

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.

The effect of short term exposure to outdoor air pollution on fertility.

BACKGROUND: There is evidence to suggest that long term exposure to air pollution could be associated with decreased levels of fertility, although there is controversy as to how short term exposure may compromise fertility in IVF patients and what windows of exposure during the IVF process patients could be most vulnerable. METHODS: This prospective cohort study aimed to evaluate the impact of acute exposure that air pollution have on reproductive outcomes in different moments of the IVF process. Women undergoing IVF living in Barcelona were recruited. Individual air pollution exposures were modelled at their home address 15 and 3 days before embryo transfer (15D and 3D, respectively), the same day of transfer (D0), and 7 days after (D7). The pollutants modelled were: PM2.5 [particulate matter (PM) ≤2.5 µm], PMcoarse (PM between 2.5 and 10µm), PM10 (PM≤10 µm), PM2.5 abs, and NO2 and NOx. Outcomes were analyzed using multi-level regression models, with adjustment for co-pollutants and confouding factors. Two sensitivity analyses were performed. First, the model was adjusted for subacute exposure (received 15 days before ET). The second analysis was based on the first transfer performed on each patient aiming to exclude patients who failed previous transfers. RESULTS: One hundred ninety-four women were recruited, contributing with data for 486 embryo transfers. Acute and subacute exposure to PMs showed a tendency in increasing miscarriage rate and reducing clinical pregnancy rate, although results were not statistically significant. The first sensitivity analysis, showed a significant risk of miscarriage for PM2.5 exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 on 3D. The second sensitivity analysis showed a significant risk of miscarriage for PM2.5 exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PMcoarse and PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes. CONCLUSIONS: Exposure to particulate matter has a negative impact on reproductive outcomes in IVF patients. Subacute exposure seems to increase the harmful effect of the acute exposure on miscarriage and pregnancy rates. Nitrogen dioxides do not modify significantly the reproductive success.

Impact of maternal education level on live birth rate after in vitro fertilization in China: a retrospective cohort study.

PURPOSE: To assess the association between maternal education level and live birth after in vitro fertilization (IVF). METHODS: We studied women who underwent the first cycle of fresh or frozen-thawed embryo transfer between 2014 and 2019. Women were divided into four educational categories according to the level of education received (elementary school graduate or less, middle school graduate, high school graduate, college graduate or higher). The live birth rate was compared between different education level groups. We used logistic regression to analyze the association between maternal education level and live birth after IVF. RESULTS: We studied 41,546 women, who were grouped by maternal educational level: elementary school graduate or less (n = 1590), middle school graduate (n = 10,996), high school graduate (n = 8354), and college graduate or higher (n = 20,606). In multivariable logistic regression analysis, we did not demonstrate a statistically significant relationship between educational level and live birth in middle school graduate (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.84-1.09), high school graduate (AOR 1.01; 95% CI, 0.87-1.14) or college graduate or higher (AOR 1.01; 95% CI, 0.88-1.14) patients, with elementary school graduate or less as the reference group. CONCLUSIONS: Maternal educational level was not associated with the likelihood of live birth in patients undergoing fresh or frozen embryo transfer.