Obstetric and Perinatal Outcomes following Ovulation Induction and Unassisted Pregnancies in the Same Mother.

OBJECTIVE: We aimed to assess whether ovulation induction treatments affect obstetric and neonatal outcomes. STUDY DESIGN: This was a historic cohort study of deliveries in a single university-affiliated medical center between November 2008 and January 2020. We included women who had one pregnancy following ovulation induction and one unassisted pregnancy. The obstetric and perinatal outcomes were compared between pregnancies following ovulation induction and unassisted pregnancies, so that each woman served as her own control. The primary outcome measure was birth weight. RESULTS: A total of 193 deliveries following ovulation induction and 193 deliveries after unassisted conception by the same women were compared. Ovulation induction pregnancies were characterized by a significantly younger maternal age and a higher rate of nulliparity (62.7 vs. 8.3%, p < 0.001). In pregnancies achieved by ovulation induction, we found a higher rate of preterm birth (8.3 vs. 4.1%, p = 0.02) and instrumental deliveries (8.8 vs. 2.1%, p = 0.005), while cesarean delivery rates were higher following unassisted pregnancies. Birth weight was significantly lower in ovulation induction pregnancies (3,167 ± 436 vs. 3,251 ± 460 g, p = 0.009), although the rate of small for gestational age neonates was similar between the groups. On multivariate analysis, birth weight remained significantly associated with ovulation induction after adjustment for confounders, while preterm birth did not. CONCLUSION: Pregnancies following ovulation induction treatments are associated with lower birth weight. This may be related to an altered placentation process following uterine exposure to supraphysiological hormonal levels. KEY POINTS: · Ovulation induction entails lower birthweight.. · This may relate to supraphysiological hormonal levels.. · Monitoring fetal growth is advised in such cases..

Can endocrine characteristics of early pregnancy following natural cycle cryopreserved embryo transfer predict live birth?

RESEARCH QUESTION: Can serial measurements of serum oestradiol, progesterone and ß-human chorionic gonadotrophin (HCG) concentrations, starting from the day of the first positive pregnancy test, predict live birth after natural cycle frozen-thawed embryo transfer (NC-FET)? DESIGN: This was a historical cohort study of women with a positive pregnancy test following NC-FET, between March 2009 and January 2020. Serum ß-HCG, oestradiol and progesterone concentrations were measured on the day of the first pregnancy test and 48 and 96 h later. Pregnancies resulting in a live birth were compared with non-viable pregnancies. RESULTS: Of 101 women with a positive pregnancy test included in the study, 78 had a live birth and 23 had a non-viable pregnancy. Serum ß-HCG concentrations were comparable on the day of the first pregnancy test (P = 0.09) but became significantly higher in women with a live birth 48 and 96 h later (P = 0.018 and P = 0.003). Serum oestradiol concentrations were higher in women with a live birth at all three measurements (P = 0.02, P = 0.007 and P = 0.02). Serum progesterone concentrations were higher 48 h after the first pregnancy test in women with a live birth (P = 0.04). On multivariate analysis, after controlling for the women's ages and number of embryos transferred, serum concentrations above the 25th percentile for oestradiol (>488-526 pmol/L) and progesterone (>63-70 nmol/L) were independent predictors of live birth at all three measurements. CONCLUSIONS: Increased serum oestradiol and progesterone concentrations in early NC-FET pregnancies are associated with increased likelihood of live birth. Oestradiol and progesterone concentrations can be used in conjunction with ß-HCG to predict pregnancy viability and assist in patient counselling.

The effect of SARS-CoV-2 mRNA vaccination on AMH concentrations in infertile women.

RESEARCH QUESTION: Does SARS-CoV-2 mRNA vaccination affect the ovarian reserve of infertile women undergoing IVF? DESIGN: This was a prospective observational study at a single university-affiliated IVF unit that included infertile women aged 18-44 years who were undergoing IVF/intracytoplasmic sperm injection between November 2020 and September 2021, had received two doses of SARS-CoV-2 mRNA vaccination and had undergone measurement of baseline anti-Müllerian hormone (AMH) concentration within the 12 months preceding their recruitment. AMH concentrations before and after vaccination were evaluated and compared. RESULTS: Overall, 31 women were included in the study. The median AMH concentrations before and after COVID-19 vaccine were comparable (1.7 versus 1.6 g/ml, respectively, P = 0.96). No correlation was found between the participant's anti-COVID-19 antibody titre and the change in AMH concentration. CONCLUSIONS: SARS-CoV-2 mRNA vaccination does not adversely affect ovarian reserve, as shown by comparing serum AMH concentrations before and after vaccination. These findings may serve as a counselling tool for clinicians to reassure women undergoing fertility treatment that SARS-CoV-2 mRNA vaccination is safe.

Obstetric outcomes following ovarian hyperstimulation syndrome in IVF - a comparison with uncomplicated fresh and frozen transfer cycles.

BACKGROUND: We aimed to assess the correlation between ovarian hyperstimulation syndrome (OHSS) in the early course of in vitro fertilization (IVF) pregnancies and obstetric outcomes. METHODS: We identified records of patients admitted due to OHSS following IVF treatment at our institution between 2008 and 2020. Cases were included if pregnancy resulted in a live singleton delivery (OHSS group). OHSS cases were matched at a 1:5:5 ratio with live singleton deliveries following IVF with fresh embryo transfer (fresh transfer group) and frozen embryo transfer (FET group), according to maternal age and parity. Computerized files were reviewed, and maternal, obstetric and neonatal outcomes compared. RESULTS: Overall, 44 OHSS cases were matched with 220 fresh transfer and 220 FET pregnancies. Patient demographics were similar between the groups, including body mass index, smoking and comorbidities. Gestational age at delivery, the rate of preterm births, preeclampsia and cesarean delivery were similar between the groups. Placental abruption occurred in 6.8% of OHSS pregnancies, 1.4% of fresh transfer pregnancies and 0.9% of FET pregnancies (p=0.02). On post-hoc analysis, the rate of placental abruption was significantly higher in OHSS pregnancies, compared with the two other groups, and this maintained significance after adjustment for confounders. Birthweights were 3017 ± 483, 3057 ± 545 and 3213 ± 542 grams in the OHSS, fresh transfer and FET groups, respectively (p=0.004), although the rate of small for gestational age neonates was similar between the groups. CONCLUSIONS: OHSS in the early course of IVF pregnancies is associated with an increased risk of placental abruption.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

PURPOSE: This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. METHODS: PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. RESULTS: Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. CONCLUSION: Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Misoprostol treatment for early pregnancy loss: an international survey.

RESEARCH QUESTION: What is the global variability in misoprostol treatment for the management of early pregnancy loss (EPL)? DESIGN: An international web-based survey of fertility specialists and obstetrics and gynaecology clinicians was conducted between August and November 2020. The survey consisted of 16 questions addressing several aspects of misoprostol treatment for EPL. RESULTS: Overall, 309 clinicians from 80 countries participated in the survey, of whom 67.3% were fertility specialists. Nearly one-half (47.9%) of the respondents let the patient choose the first line of treatment (expectant management, misoprostol treatment or surgical aspiration) according to her own preference. The 248 respondents who administer misoprostol in their daily practice were asked further questions; 59.7% of them advise patients to take the medication at home. The most common dose and route of administration is 800 µg administered vaginally. Only 28.6% of participants use mifepristone pretreatment. Variation in the timing of the first follow-up visit after misoprostol administration was wide, ranging from 24 h to 1 week in most clinics. In case of incomplete expulsion, only 42.3% of the respondents routinely administer a second dose. The timing of the final visit and the definition of successful treatment also differed greatly among respondents. CONCLUSIONS: There is large variability in the use of misoprostol for the management of EPL. High-quality research is necessary to examine several aspects of the treatment. Particularly, the timing and effectiveness of a second dose administration and the criteria to decide on treatment failure or success deserve more research in the future.

Placental disorders of pregnancy in subsequent IVF pregnancies - a sibling cohort.

RESEARCH QUESTION: To assess whether the incidence of placental disorders of pregnancy decreases with increasing parity in repeat IVF pregnancies, in the same way as natural pregnancies. DESIGN: This was a retrospective cohort of deliveries between November 2008 and January 2020, in a single university-affiliated medical centre. The study included women with only IVF-attained singleton pregnancies (no natural conception) with at least two deliveries, and compared the obstetric and perinatal outcomes between first, second and third deliveries. Each woman served as her own control. The primary outcome was the incidence of placental-related disorders of pregnancy, defined as small for gestational age (SGA) neonates and/or pre-eclampsia. RESULTS: A total of 307 first deliveries, 307 second deliveries and 49 third deliveries by the same women were compared. A trend for a decreased rate of pre-eclampsia was noted with increased parity (P = 0.06) and a significant decrease in the rate of SGA: 11.7% for first delivery, 7.8% for second delivery and 2.0% for third (P = 0.04). This difference in SGA incidence was maintained in a matched sub-analysis of the 49 women with three deliveries (P = 0.04), and after adjustment for fresh/frozen embryo transfer (P = 0.03). Although SGA and pre-eclampsia were generally more common in IVF than natural pregnancies, their decrease with increasing parity mimicked that in natural pregnancies. CONCLUSION: IVF pregnancies are associated with an increased risk of placental disorders of pregnancy. However, they exhibit a decrease in incidence with increasing parity.

A randomized controlled trial of vaginal progesterone for luteal phase support in modified natural cycle - frozen embryo transfer.

OBJECTIVE: Our aim was to study whether luteal phase support (LPS) increases the live-birth rate (LBR) in women undergoing modified natural cycle (mNC) frozen-thawed embryo transfer (FET). METHODS: In a randomized controlled trial, conducted at a university-affiliated tertiary medical center, a total of 59 patients aged 18-45 years, underwent mNC-FET. FET was performed in mNC following ovulation triggering by hCG. Patients were randomized into two groups; The No-LPS Group included 28 women who did not receive LPS, and the LPS Group included 31 women who received vaginal progesterone for LPS. The main outcome measure was LBR. RESULTS: Baseline demographic and clinical characteristics were comparable between the study groups. The no-LPS group and the LPS group did not differ with regard to clinical pregnancy rate (21.4% vs. 32.3%; respectively, p = .35), LBR (17.9% vs. 19.4%; respectively, p = .88), or spontaneous miscarriage rate (3.6% vs. 12.9%; respectively, p = .35). On multivariate logistic regression analysis, LPS was not associated with LBR after controlling for confounders. CONCLUSION: The results of our study suggest that LPS after mNC-FET does not improve the reproductive outcome, and therefore, might not be necessary.C linicaltrials.gov identifier: NCT01483365.

Does the interval between the last GnRH antagonist dose and the GnRH agonist trigger affect oocyte recovery and maturation rates?

RESEARCH QUESTION: Does the time interval between the last gonadotrophin-releasing hormone (GnRH) antagonist dose and the GnRH agonist trigger affect the efficacy of the trigger in IVF treatments? DESIGN: This retrospective cohort study involved 53 normogonadotrophic patients undergoing GnRH antagonist-based IVF cycles, in a single academic centre between June 2019 and February 2020, in whom a GnRH agonist was used for final ovulation triggering. RESULTS: The mean time interval between the last GnRH antagonist dose and GnRH agonist triggering was 4.6 ± 2.7 h (range 1-12 h). There was no correlation between the antagonist-agonist interval and the oocyte recovery rate (Spearman's correlation coefficient [CC] 0.02, P = 0.89) or metaphase II oocyte rate (CC 0.006, P = 0.96). On multivariate analysis, the antagonist-agonist interval was not associated with treatment outcomes, after adjusting for the women's age and body mass index. CONCLUSIONS: This is the first study assessing the efficacy of the GnRH agonist trigger in relation to the time interval between the last GnRH antagonist dose and the agonist trigger within the first half-life of the GnRH antagonist and in less than 12 h. In normogonadotrophic patients, a GnRH agonist trigger can successfully induce an effective LH surge and oocyte maturation and release, irrespective of the time interval between the last antagonist dose and the agonist trigger. Once confirmed by randomized clinical trials, these finding may simplify treatment, improve patients' convenience and promote patient adherence to treatment.

Reproductive outcome after early pregnancy loss treated with misoprostol versus surgical aspiration.

RESEARCH QUESTION: Does long-term reproductive outcome after early pregnancy loss (EPL) differ between women who are treated with misoprostol and surgical aspiration. DESIGN: A historic cohort study of all women who were diagnosed with early pregnancy loss (≤12 weeks), in a single medical centre, between September 2016 and August 2017, was conducted. The women were treated with either misoprostol or surgical aspiration according to their own preferences. Women who were lost to follow-up or did not attempt to conceive again were excluded. The primary outcome measure was the cumulative pregnancy rate within 12 months from intervention. RESULTS: Baseline characteristics were comparable between women who received misoprostol (n = 163) and women who underwent surgical aspiration (n = 122). Women who received misoprostol had a higher rate of interventions for retained products of conception (11.0% versus 3.3%, respectively; P = 0.015). The misoprostol and the surgical aspiration groups did not differ in rate of repeated miscarriages (17.8% versus 21.3%, respectively; P = 0.45), or pregnancy rate within 6 months (58.3% versus 50.0%, respectively; P = 0.16), 12 months (78.5% versus 78.7%, respectively; P = 0.97) and 24 months (92.0% versus 91.8%, respectively; P = 0.94). Live birth rate within 24 months was comparable (62.0% versus 58.2%, respectively; P = 0.52), as well as gestational age at birth (38.5 versus 38.6 weeks, respectively; P = 0.81) and birthweight (3295 versus 3161 g, respectively; P = 0.07). CONCLUSIONS: Long-term reproductive outcomes are comparable in women with EPL who are treated with either misoprostol or surgical aspiration. Our findings may help counselling patients facing EPL who have concerns about their future reproduction.