Safety and Efficacy of Cervical Ripening and Induction of Labor Using Prostaglandin E1 in Primiparas, Multiparas and Grand Multiparas.

Objective: To compare the efficacy and safety of cervical ripening and induction of labor with prostaglandin E1 among primiparas, multiparas and grand multiparas. Study design: This was a retrospective cohort study. Results: Between January and December 2017, 1713 women underwent cervical ripening and induction of labor with prostaglandin E1: 523 were primiparas, 656 were multiparas, and 534 were grand multiparas. Four hundred and seventy-nine (91.6%) primiparas delivered vaginally as did 640 (97.6%) multiparas and 521 (97.6%) grand multiparas. Forty-four (8.4%) primiparas underwent cesarean delivery compared to 16 (2.4%) multiparas and 13(2.4%) grand multiparas. Induction to delivery interval was significantly longer in primiparas (29.7 ± 22.8 h). There were no cases of uterine rupture, and the rates of postpartum hemorrhage and endometritis were similar among the three groups. Neonatal outcomes including Apgar score < 7 and umbilical artery pH < 7.1 were not significantly different between the groups. Conclusion: Using prostaglandin E1 for cervical ripening and labor induction is efficient and safe in primiparas, multiparas and grand multiparas.

Cleavage Patterns of 9600 Embryos: The Importance of Irregular Cleavage.

This prospective, observational study investigated the incidence of irregular cleavage (IRC) among human embryos and its influence on IVF treatment outcomes. It included 1001 women who underwent 1976 assisted reproduction treatments during 2016-2021 in a single IVF clinic. Embryo morphokinetics were analyzed and evaluated for the association between IRC and women's characteristics, treatment characteristics, and pregnancy outcomes. The incidence of IRC was 17.5% (1689/9632 embryos). Of these, 85% of the embryos had one IRC, 15% had multiple IRC and 35% of IRC events occurred during the embryo's first cell cycle. IRC embryos were found to correlate with male factor (p = 0.01) and higher ICSI rate (p = 0.01). Age, BMI, parity, basal FSH level, stimulation protocol, and number of retrieved oocytes did not differ between groups. Embryos with early IRC or more than one IRC had lower blastulation rates (p = 0.01 for each). Fresh cycles with IRC embryos had a lower clinical pregnancy rate (p = 0.01) and embryos with early IRC had a lower live birth rate (p = 0.04) compared to embryos without IRC. Frozen transfer cycles of blastocyst embryos, with or without IRC, had comparable results. In conclusion, the number of abnormal cleavage events and their timing are important factors in the prognosis of the developing human embryo.

High initial ß-hCG predicts IVF outcomes accurately and precludes the need for repeated measurements.

This study evaluated ß-human chorionic gonadotropin (hCG) changes during the early period of pregnancy in an attempt to predict successful pregnancy outcomes in ART. It determined the median values of the ß-hCG and the 2-day ß-hCG increments of clinical vs biochemical pregnancies. The results of fresh day 3 embryo, frozen day 3 embryo, and frozen day 5 embryo transfers were evaluated. The cutoff values of ß-hCG and the 2-day increments predicting clinical pregnancy and delivery were determined. All women who underwent embryo transfer and had a singleton pregnancy from January 2017 to December 2019 were included. As expected, clinical pregnancies had higher initial median ß-hCG values compared to biochemical pregnancies (fresh day 3 (400 vs 73 mIU/mL), frozen day 3 (600 vs 268.5 mIU/mL) and frozen day 5 (937 vs 317 mIU/mL)). Nonetheless, the abortion rate was significantly lower in the group with ß-hCG above the cutoff values in fresh (141 mIU/mL) and frozen (354.5 mIU/mL) cleavage stage transfers (17.2% vs 44%, P < 0.001 and 18.5% vs 38%, P = 0.003, respectively). Blastocyst transfers resulted in higher median initial ß-hCG compared to cleavage embryo transfers (937 vs 600 mIU/mL), and the initial ß-hCG values from frozen cleavage embryos were higher compared to fresh cleavage embryos (600 vs 400 mIU/mL). Earlier implantation in frozen cycles may be caused by freezing-thawing procedures. Moreover, in fresh cycles, negative effects of the hormonal milieu of fresh cycles may delay implantation. These results indicate that high initial ß-hCG and high 2-day ß-hCG increments demonstrated better outcomes, including more clinical pregnancies and fewer abortions.

Ovulatory-cycle frozen embryo transfer: spontaneous or triggered ovulation and the impact of LH elevation at hCG triggering.

The effect of the luteinizing hormone (LH) elevation before the human chorionic gonadotropin (hCG) trigger in ovulatory frozen-thawed embryo transfer (Ovu-FET) cycles has not been determined. We aimed to investigate whether triggering ovulation in Ovu-FET cycles affects the live birth rate (LBR), and the contribution of elevated LH at the time of hCG trigger. This retrospective study included Ovu-FET cycles performed in our center from August 2016 to April 2021. Modified Ovu-FET (hCG trigger) and true Ovu-FET (without hCG trigger) were compared. The modified group was divided according to whether hCG was administered, before or after LH increased to > 15 IU/L and was twice the baseline value. The modified (n = 100) and true (n = 246) Ovu-FET groups and both subgroups of the modified Ovu-FET, those who were triggered before (n = 67) or after (n = 33) LH elevation, had comparable characteristics at baseline. Comparison of true vs. modified Ovu-FET outcomes revealed similar LBR (35.4% vs. 32.0%; P = 0.62), respectively. LBR were similar between the modified Ovu-FET subgroups regardless of the hCG trigger timing (31.3% before vs. 33.3% after LH elevation; P = 0.84). In conclusion, LBR of Ovu-FET were not affected by hCG trigger or whether LH was elevated at the time of hCG trigger. These results add reassurance regarding hCG triggering even after LH elevation.

Predictive Factors for Successful Vaginal Delivery after a Trial of External Cephalic Version: A Retrospective Cohort Study of 946 Women.

OBJECTIVE: Our aim was to find the factors which predict a vertex presentation of vaginal delivery (VD) in women who are admitted for a trial of external cephalic version (ECV). STUDY DESIGN: This is a retrospective cohort study of women who underwent a trial of ECV and delivered between November 2011 and December 2018 in a single tertiary center. The main outcome measure was successful VD of a fetus in the vertex presentation. Women who achieved VD in the vertex presentation or underwent cesarean delivery were compared on the basis of variety of predictive factors. Adverse neonatal and maternal outcomes were reported. Logistic regression was used for the multivariate analysis. RESULTS: A total of 946 women were included; 717 (75.8%) women had a successful ECV and 663 (70.1%) women had a VD in the vertex presentation. Parous women had 79.3% VD rate (570/719) and nulliparous women had 41.0% VD rate (93/227). Women with an amniotic fluid index (AFI) of 50 to 79, 80 to 200, and >200 mm had 34.8, 71.0, and 83.1% VD rate, respectively. Parous versus nulliparous women had an adjusted odds ratio (aOR) of 5.42 (95% confidence interval [CI]: 3.90-7.52, p < 0.001), women with AFI 50 to 79 mm compared with AFI 80 to 200 mm had an aOR of 0.21 (95% CI 0.12-0.37, p < 0.001), and women with an AFI >200 mm compared with AFI 80 to 200 mm had an aOR of 1.74 (95% CI: 1.03-2.92, p = 0.037) to achieve VD. The final prediction model for the chances of a VD based on data on admission for ECV was reported. The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model (p = 0.836). CONCLUSION: Being parous and having an AFI >200 mm are positive independent predictive factors for achieving VD of a vertex presenting fetus after ECV. Whereas AFI 50 to 79 mm is a negative independent predictive factor. KEY POINTS: · The goal of ECV is to achieve a vertex VD.. · Predictors for ECV success might not predict a VD.. · Parity & AFI independently predict a VD after ECV..

The Impact of Lifestyle on Sperm Function, Telomere Length, and IVF Outcomes.

Many risk factors can potentially influence sperm quality. Telomeres confer stability on the chromosome and their dysfunction has been implicated in conditions such as cancer, aging, and lifestyle. The impact of lifestyle on sperm cell telomeres is unclear. The objectives of this study were to evaluate the impact of lifestyle behaviors on telomere length in sperm and to follow the correlation with pregnancy outcomes in patients undergoing in vitro fertilization (IVF). In this prospective observational study, sperm was analyzed for telomere length (TL). Men were asked to report lifestyle behaviors including occupation (physical or sedentary), smoking duration and amount, physical activity, dietary habits, and where they keep their cellular phone (bag, pants, or shirt pocket). Correlations among semen analysis, TL, men's habits, and embryo quality and pregnancy outcomes were evaluated. Among 34 patients recruited, 12 had longer TL and 13 shorter TL. Sperm motility was negatively correlated with TL (Pearson correlation = -.588, p = .002). Smoking adversely affected native sperm motility (53% motility in nonsmokers vs. 37% in smokers; p = .006). However, there was no significant impact on TL. The group with longer telomeres demonstrated significant association with healthy diet (10/12 vs. 6/13; p = .05) and a trend toward more sports activity, weekly (16/84 vs. 7/91; p = .04) compared with the shorter telomeres group. This study suggests that lifestyle, healthy diet, and sports activity are associated with long telomeres in sperm. Sperm quality is also influenced by patients' habits. The study strongly recommends maintaining a healthy lifestyle to preserve general health and fertility.

Embryonic Development in Relation to Maternal Obesity Does Not Affect Pregnancy Outcomes in FET Cycles.

This retrospective cohort study examined the effect of maternal BMI on embryo morphokinetics using a time-lapse incubator (TLI) and evaluated the effect on outcomes of frozen embryo transfer (FET) cycles. The study included 641 women who underwent FET of a total of 2553 embryos from January 2017 to August 2019. The women were divided into four groups according to BMI: underweight (<18.5 kg/m2), normal weight (18.5−24.99 kg/m2), overweight (25.0−29.99 kg/m2), and obese (≥30 kg/m2). Embryos were transferred on day 3 or 5, and their development was monitored using a TLI. We found that oocytes from obese patients were slower in the extraction of the second polar body (tPB2) after fertilization and the two pronucleus stage appeared later compared to normal-weight women. The time to fading of the pronucleus (tPNf), t2, and t4 were comparable between the four groups. Oocytes from underweight and overweight women had significantly faster cleavage at t3 and t5−t8 compared to normal weight. We did not find any significant difference in pregnancy rate, clinical pregnancy rate, or miscarriage rate among groups. In conclusion, embryos from normal-weight patients had slower cleavage rates compared to obese patients, while embryo quality was similar between BMI groups. The cycle outcomes demonstrated comparable pregnancy rates among the BMI groups.

Does mRNA SARS-CoV-2 vaccine in the follicular fluid impact follicle and oocyte performance in IVF treatments?

PROBLEM: The COVID-19 pandemic has many clinical manifestations. Rapid vaccine development raised concerns and speculations about future fertility outcomes and vaccine safety. We evaluated the effect of Pfizer-BioNTech mRNA SARS-CoV-2 vaccine on IVF treatment, oocyte and embryo quality, and pregnancy outcomes. METHOD OF STUDY: This prospective, observational cohort study was conducted in a referral IVF Unit, 3/2021-5/2021. We aimed to recruit all women undergoing IVF/ICSI cycles from 3/1-4/30/2021, 2-8 weeks after the second vaccination, and to analyze 50-60 samples in the 2-month period. Patients were categorized according to serum antibody levels: positive for spike (S), positive for nucleotide (N), or negative for both. On the day of ovum pick-up, follicular fluid and blood samples were analyzed for anti-nucleotide (anti-N) antibodies, and anti-spike (anti-S) antibodies, hormonal profile, C-reactive protein (CRP) and other metabolic parameters. RESULTS: Of 59 women enrolled, 37 reported being vaccinated and 22 were not. We found 97% correlation between anti-S and anti-N in the blood and the follicular fluid. Follicular fluid was analyzed based on antibody categorization. All IVF treatment parameters in the follicular fluids and serum were comparable, except CRP was significantly elevated among patients with anti-N antibodies (2.29 [1.42-6.08] vs. 4.11 [1.62-5.75] vs. 1.44 [.36-8.33]; p < .001). Pregnancy outcomes were comparable (44% vs. 33% vs. 50%; p = .97). CONCLUSION: mRNA SARS-CoV-2 vaccine did not appear to affect treatment outcomes or ovarian reserves in the subsequent IVF cycle.

Male genome influences embryonic development as early as pronuclear stage.

BACKGROUND: Impaired paternal genome expression may cause poor embryonic development after in vitro fertilization (IVF). OBJECTIVE: To evaluate the expression of male infertility on embryo morphokinetics using a time-lapse incubator and its impact on IVF cycles. MATERIALS AND METHODS: This retrospective cohort study followed patients from January 2017 to August 2019. Patients were divided according to the cause of infertility to male factor (study group) and unexplained infertility (control group) and further subdivided according to the severity of male infertility. RESULTS: A cohort of 462 patients who underwent IVF cycles, with a total of 3,252 embryos was evaluated. Intracytoplasmic sperm injection (ICSI) was conducted more often in the study group compared to the control group (94% vs. 47%, p < 0.0001) and more embryos were discarded (47% vs. 43%, p = 0.016). Treatment outcomes were comparable in both groups regardless of the severity of male infertility. T3-T5 had a significant impact on embryo quality and more transfer and freeze compared to discard. Maternal age, number of aspirated oocytes, BMI, protocol used, and faster time to T3, T6 were significant in increasing chances of achieving pregnancy. CONCLUSION: The paternal genome may have an earlier impact on embryo development than previously surmised and may also account for faster morphokinetics. Faster embryo cleavage in male infertility IVF-ICSI cycles may contribute to outcomes comparable to other causes of infertility, in terms of embryo quality and clinical pregnancy rate, despite lower sperm quality, even in cases of severe Oligo-terato-Astheno spermia (OTA).

Diode Laser Hysteroscopic Metroplasty for Dysmorphic Uterus: a Pilot Study.

This paper aims to study the efficacy and safety of diode laser hysteroscopic metroplasty for dysmorphic uterus and the impact on reproductive outcomes. This is a retrospective, single-center pilot study with prospective follow-up. The study was performed at a university-affiliated, tertiary hospital. From February 2018 to February 2020, all nulliparous women with a 3D ultrasound diagnosis of T-shaped or Y-shaped dysmorphic uterus and diagnosis of infertility, recurrent implantation failure, or recurrent pregnancy losses were referred for hysteroscopic metroplasty. Diode laser hysteroscopic metroplasty was performed under general anesthesia in an ambulatory setting. Main outcome measures included operative time, complications, hysteroscopic appearance of the cavity in a follow-up hysteroscopy, and reproductive outcomes in terms of pregnancy and live birth. A total of 25 infertile women with mean duration of infertility of 56.6 ± 36.1 months underwent hysteroscopic metroplasty. No complications were reported, and subsequent 3D ultrasound and follow-up hysteroscopic appearance were satisfactory in all cases. Maximum follow-up was 32 months (mean ± standard deviation 11.5 ± 9.2 months). Fifteen nulliparous women returned for fertility treatments in our institute, among whom nine conceived (60% pregnancy rate). The rate of deliveries and ongoing pregnancies (pregnancies beyond 24 weeks of gestation) was 78% (7/9), with six successful liveborn deliveries at 36-38 weeks and one ongoing pregnancy. One had spontaneous abortion at week 19 and one had a spontaneous abortion at week 7. Hysteroscopic metroplasty in an ambulatory setting, using diode laser, is a safe and effective procedure, improving reproductive outcomes in cases of T-shaped or Y-shaped uterus.

Ovulatory-Based FET Cycles May Achieve Higher Pregnancy Rates in the General Population and among Anovulatory Women.

This study evaluated which endometrial preparation protocol in frozen embryo transfer (FET) cycles provides the best results for polycystic ovarian syndrome (PCOS) patients and the general population. This retrospective study of 634 FET cycles was conducted 2016-2018. Cycles were divided into Group A: Artificial endometrial preparations for FET (aFET; n = 348), Group B: Ovulatory cycle (n = 286) to compare two methods of endometrial preparation for FET. Artificial endometrial preparation with exogenous estrogen and progesterone versus natural ovulation cycles, modified natural cycles using hCG for the final triggering and letrozole-induced ovulation with hCG. Anovulatory patients were analyzed separately. Anovulatory PCOS patients had significantly higher pregnancy rates with letrozole treatment compared with aFET cycles (44% vs. 22.5%; p = 0.044). For the entire cohort, ovulatory cycles and aFET were similar in terms of patient characteristics, demographics, infertility causes, treatment protocols and number of embryos transferred. Although the mean ESHRE score of the transferred embryos was higher in the aFET group, we found higher clinical pregnancy rate in the ovulatory cycle FET (41.3% vs. 27.3%, p < 0.0001). A better pregnancy rate was found after ovulatory cycle FET. In the ovulatory cycles, the outcome of letrozole-induced and non-induced cycles were comparable. PCOS patients, as well as the general population, may benefit from ovulation induced FET cycles, with significantly better outcomes in FET in ovulatory cycles.

Transfer of Day 6 Frozen-Thawed Blastocysts on Day 5 Compared with Day 6: Catching Up with the Window of Implantation-a Retrospective Study.

To compare clinical pregnancy rate (CPR) and live birth rate (LBR) after frozen-thawed embryo transfer (FET) of day (D-) 6 blastocysts on D-5 versus D-6. A retrospective cohort study. A university-affiliated single-center tertiary hospital. Women undergoing FET of D-6 blastocysts between August 2015 and March 2019 were included in the study. Exclusion criteria were endometriosis and maternal age ≥ 42. Cycles involving embryo transfer (ET) at D-6 were compared to cycles involving ET on D-5. Primary outcomes assessed were CPR and LBR, and the secondary outcomes were spontaneous abortion and chemical pregnancy rates. Forty-two cycles were assessed, 21 in which ET occurred on D-6 and 21 in which ET occurred on D-5. There were no significant differences between groups regarding age, body mass index (BMI), etiology of infertility, number of oocytes aspirated and blastocysts cryopreserved in the fresh cycle, reason for freezing on D-6, endometrial thickness before ET, and blastocyst grade. A comparison of outcomes of ET on D-5 with those involving ET on D-6 revealed that D-5 transfer produced significantly higher CPR (8, 38% vs. 2, 8.5%; P = 0.030) and LBR (6, 28.6% vs. 1, 4.8%; P = 0.038), respectively. FET of D-6 embryos on D-5 compared with D-6 is associated with increased CPR and LBR values. These findings might be related to the limited time window for optimal rates of implantation and indicate that transferring embryos on D-6 of a FET cycle is likely too late.

Comparable Outcomes Using Oral Dydrogesterone Vs. Micronized Vaginal Progesterone in Frozen Embryo Transfer: a Retrospective Cohort Study.

This retrospective study was conducted to determine whether using oral dydrogesterone (DYD) instead of micronized vaginal progesterone (MVP) in frozen embryo transfer (FET) cycles affects pregnancy outcomes. Women undergoing autologous FET in an academic fertility center were evaluated. Uses of 10 mg TID oral DYD or MVP for patients treated in FET cycles (artificial and ovulatory cycle, separately) were compared. The main outcome measure was live birth rates in each group. The study analyzed 599 cycles that occurred from January 2018 through December 2019. Chemical and clinical pregnancy rates were comparable between DYD vs. MVP groups (41.6% vs. 38.1%; P = 0.44 and 36.7% vs. 31.4%; P = 0.18, respectively). The ongoing pregnancy and delivery rates (29% vs. 22%, P = 0.06), as well as abortion rate (12.3% vs. 15.8%, P = 0.2), were comparable between the two groups. In a case-control sub-analysis of artificial FET cycles, we found comparable results between the two modes of luteal support. Similarly, results were comparable in ovulatory cycles using these medications for luteal support. Chemical and clinical pregnancy rates were comparable with DYD vs. MVP, in artificial FET (33.7% vs. 34.8%; P = 0.89 and 27.7% vs. 27.5%; P = 1), and in ovulatory FET (46.5% vs. 43.9%; P = 0.71 and 42.3% vs. 38.2%; P = 0.53), respectively. Our results indicate that in FET, pregnancy outcomes with oral DYD were not inferior to those with MVP.