High prevalence of low prognosis by the POSEIDON criteria in women undergoing planned oocyte cryopreservation.

OBJECTIVE: Planned oocyte cryopreservation (OC) is being increasingly utilized worldwide. However, some women cannot accumulate sufficient oocytes because of poor response to stimulation. The POSEIDON classification is a novel system to classify patients with 'expected' or 'unexpected' inappropriate ovarian response to exogenous gonadotropins. Our study aimed to examine the prevalence of POSEIDON patients among women undergoing planned OC. STUDY DESIGN: We retrospectively reviewed the first cycles of 160 consecutive patients undergoing planned OC. Patients were classified into the four POSEIDON groups or as 'non-POSEIDON' based on age, AMH level and the number of oocytes retrieved. The primary outcome measure was the prevalence of POSEIDON patients. RESULTS: Overall, 63 patients (39.4 %) were classified as POSEIDON patients, 12 in group 1, 12 in group 2, 8 in group 3, and 31 in group 4. Compared to non-POSEIDON patients, POSEIDON patients had increased basal FSH levels and reduced serum AMH levels and antral follicle counts, required higher FSH starting doses and increased gonadotropin requirements and reached lower peak serum estradiol levels. Additionally, POSEIDON patients had a lower number of oocytes retrieved (7.6 ± 3.1 vs.20.2 ± 9.9, p < 0.001) and vitrified (5.8 ± 2.9 vs.14.7 ± 6.8, p < 0.001) than non-POSEIDON counterparts, respectively. CONCLUSION: We found a high prevalence of patients being classified as low prognosis according to the POSEIDON criteria among patients seeking planned OC. POSEIDON patients had increased gonadotropin requirements and a significantly lower number of oocytes retrieved and vitrified. This novel, unexpected finding adds clinically relevant information for counselling and management of patients undergoing planned OC.

Placenta previa in in vitro fertilization and unassisted pregnancies-is there a difference in perinatal outcomes and placental histology?

INTRODUCTION: In-vitro-fertilization (IVF) is an independent risk factor for placenta previa (PP). Our aim was to study this link by comparing the clinical characteristics and placental histology of pregnancies complicated by PP in IVF versus unassisted pregnancies. METHODS: A retrospective-cohort study of deliveries with PP between 2008 and 2021. Placental histology, obstetric and neonatal outcomes were compared between IVF and unassisted pregnancies. Included, were singleton deliveries complicated by PP at gestational weeks (GA) >24. RESULTS: A total of 182 pregnancies were included - 23 IVF pregnancies (IVF group) and 159 unassisted pregnancies (Control group). The control group was characterized by higher gravidity (p = .007) and parity (p < .001) and a trend of more past cesarean deliveries, whereas the IVF group- by a higher rate of nulliparity (p < .001) and diabetes mellitus (p = .04). The control group was characterized by a higher rate of placental weight below the 10th percentile (47.8 versus 13.9%, p = .001) and by a trend of a lower overall placental weight. No differences were noted in maternal and fetal vascular lesions. DISCUSSION: While PP in non-assisted pregnancies is probably associated with previous CDs, in IVF it is more "sporadic," and may complicate any index pregnancy. A lower placental weight was more prevalent in the control group, supporting the concept that pregnancies complicated by PP following IVF can be attributed to initial abnormal location of placentation, rather than an underlying pathological uterine segment of implantation. Nevertheless, IVF and unassisted pregnancies entail similar perinatal outcomes in cases of PP.

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..

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.

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.

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.

Mothers' experience of their daughters' fertility problems and treatments.

Fertility treatments are a stressful experience. However, the support provided by meaningful support figures, such as a mother, may contribute positively to the mental health of women with fertility issues. The present study therefore explored the experience of Israeli mothers whose daughters encountered fertility problems and underwent treatment to bring their first child into the world. In a retrospective qualitative study, face-to-face semi-structured interviews were conducted with 16 women aged 49-73. Women in the study had a daughter in a spousal heterosexual relationship who conceived her first child via fertility treatment, and this child was up to 4 years old at the time of the interview. Three main themes emerged: (a) The stressfulness of a daughter's fertility problems and treatments for the mother; (b) The mother's supportive role; and (c) The mother's own need for support. The results suggest that due to the unique nature of the mother-daughter relationship, a daughter's fertility problems and treatments are also stressful for her mother. Nevertheless, mothers can be, and wish to be, an important source of support for their daughters. Empirically, further research to extend this understanding is recommended. Practically, professionals should be aware of the mother's distress and the fact that she is likely to deny her own need for support, and make an effort to relate to the stress of these women and help them to be a more effective resource for their daughters. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Personal growth in early pregnancy: the role of perceived stress and emotion regulation.

OBJECTIVE: Coping with the stress aroused by early pregnancy can not only result in distress, but may constitute an opportunity to experience personal growth. Relying on the model of posttraumatic growth, this study examined the contribution of perceived stress and emotion regulation to women's personal growth during the first trimester of pregnancy. METHOD: A convenience sample of Israeli women (n=170), who were during their first trimester of pregnancy (up to 13 weeks), over 18 years old, and capable to completing the instruments in Hebrew, were recruited through a women's health clinic and through social media during the years 2017-2019. RESULTS: The findings indicate that primiparous mothers report higher personal growth than multiparous. In addition, younger age, being primiparous, and higher cognitive-reappraisal contributed to greater personal growth. Moreover, a curvilinear association was found between perceived stress and personal growth, so that a medium level of stress was associated with the highest level of growth. Finally, cognitive-reappraisal fully mediated the relationship between perceived stress and personal growth. CONCLUSIONS: The findings add to the growing body of knowledge concerning the implications of early pregnancy in general, and personal growth as a result of dealing with the stress typical of this period in particular and highlight the role of the perceived stress as well as the woman's personal characteristics and resources that contribute to this result.

Gestational diabetes mellitus in in-vitro fertilization pregnancies - Clinical and placental histological characteristics.

INTRODUCTION: We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in vitro fertilization (IVF) pregnancies complicated by gestational diabetes mellitus (GDM) as compared to unassisted pregnancies. METHODS: This was a retrospective cohort of deliveries at a single university affiliated center between 12/2008 and 01/2020. Included were singleton pregnancies complicated by GDM, for which placental histopathological examination was performed. Obstetric, neonatal and placental outcomes were compared between pregnancies following IVF and unassisted pregnancies. Placental lesions were categorized according to the "Amsterdam" criteria. RESULTS: Included were 688 deliveries with a diagnosis of GDM with placental examination - 69 IVF pregnancies (IVF group) and 619 unassisted pregnancies (control group). The IVF group was characterized by a significantly higher maternal age and higher rate of nulliparous women - 60.8% vs. 32.9%, p < 0.001. There were no differences in GDM type between the study groups - about two thirds of cases were GDMA1 and on third GDMA2. A higher incidence of preeclampsia was noted in the IVF group - 17.3% vs. 9.3%, p = 0.03, with no difference in cesarean deliveries and birthweight. IVF deliveries were characterized by a significantly higher rate of adverse neonatal outcomes - 18.8% vs. 8.8%, p = 0.008, although this did not attain significance after adjustment to gestational age. No differences were noted in placental histology between the groups. DISCUSSION: GDM in IVF is associated with a significantly higher rate of adverse neonatal outcomes, as compared with non-assisted pregnancies complicated by GDM. Placental histology does not shed light on these clinical associations.

Contributors to COVID-19-Related Childbirth Anxiety among Pregnant Women in Two Pandemic Waves.

COVID-19 has impacted all levels of daily life for people everywhere, with particularly serious implications for pregnant women. This paper examines the COVID-19-related childbirth anxiety (CCA) of Israeli women in the first two waves of the pandemic. We first present two psychotherapeutic case studies with pregnant women in the two waves. This is followed by an empirical study that compared the contribution of background variables, psychological distress, economic concerns, and personal resources to CCA in two samples, Wave 1, March-April 2020 (n = 403) and Wave 2, September-October 2020 (n = 1401), and two subpopulations, Jewish and Arab women. Findings reveal that CCA was significantly lower in Wave 2 than in Wave 1. Furthermore, poorer health, higher education, being an Arab, later gestational week, at-risk pregnancy, wave, higher psychological distress, greater economic concerns, and lower self-compassion contributed to higher childbirth anxiety. Wave moderated the association between optimism and anxiety. The findings of the empirical study, together with insights from the case studies, provide evidence of a decrease in CCA later in the crisis, and indicate the significance of resources for coping with the psychological implications of the pandemic. Moreover, they suggest the importance of empowering self-reliance techniques, such as self-compassion, which was significantly associated with lower anxiety, above and beyond the background and psychological variables. Clinical Impact Statement: Using both psychotherapeutic cases and empirical findings, this study points to the risk and resilience factors that contributed to pregnant women's COVID-19-related childbirth anxiety (CCA) in the first two waves of the pandemic. The study suggests that CCA was higher in the first wave, as well as among women from a minority group. At the same time, the research shows that resilience resources of optimism and self-compassion contributed to the reduction of anxiety. These findings may guide interventions for the vulnerable group of pregnant women in times of crisis.

Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis.

BACKGROUND: Spontaneous ovulation during a natural menstrual cycle is frequently used for timing frozen embryo transfer (FET). Nevertheless, it remains unclear whether or not women should receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET). OBJECTIVE AND RATIONALE: The aim of this systematic review and meta-analysis was to study whether the administration of LPS improves the reproductive outcome following NC-FET. SEARCH METHODS: We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of the study design. The search strategy included keywords related to NC-FET and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. OUTCOMES: Our systematic search generated 416 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG and six studies (n = 1507) used progesterone for luteal support. Four studies were randomised controlled trials (RCTs), whereas the other four were historic cohort studies. In a meta-analysis using a random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (CPR) (two studies, odds ratio (OR) 0.85, 95% CI 0.64-1.14). On the other hand, progesterone LPS was associated with a higher CPR (five studies, OR 1.48, 95% CI 1.14-1.94), and a higher live birth rate (LBR) (three studies, OR 1.67, 95% CI 1.19-2.36). The association between progesterone LPS and the LBR remained significant after excluding non-randomised studies. WIDER IMPLICATIONS: The available evidence indicates that progesterone administration for LPS is beneficial following NC-FET. There is no evidence to support the administration of hCG for LPS in these cases. Additional large RCTs are necessary to improve the quality of evidence and validate our findings.

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.

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.

The stair-step approach in treatment of anovulatory PCOS patients.

Clomiphene citrate (CC) is a widely accepted first-line treatment for anovulatory patients with polycystic ovarian syndrome (PCOS). The current practice is to prescribe CC with gradual dose increments until ovulation is achieved. Typically, progesterone withdrawal bleeding is induced between each dose increment and before the commencement of gonadotropin therapy in CC-resistant patients. It has been recently suggested that dose increments of CC can be administered once failure to induce ovulation at a certain dose has been documented, without induction of progesterone withdrawal bleeding, and this approach has been nicknamed the clomiphene-citrate stair-step (CC-SS) protocol. The same principle has been found feasible before introducing gonadotropin therapy in CC-resistant PCOS patients. Our objective was to review the world literature on the CC-SS protocol and to summarize our own experience with extending the CC-SS approach to initiation of gonadotropin therapy. Studies on CC-SS protocol (n = 4) have found that this approach leads to a significant reduction of the time to ovulation and to an increased ovulation rate. In our own retrospective case series, 18 CC-resistant PCOS patients initiated gonadotropin stimulation without induction of progesterone withdrawal bleeding, using the chronic low-dose regimen. The time to ovulation in the study group was 54.2 ± 6.2 days, while the estimated time to ovulation calculated according to the traditional approach was approximately 110 days. The clinical pregnancy rate was 44% (8/18), and all pregnancies were singletons. One patient miscarried; hence, the live birth rate was 38.9% (7/18). In summary, the CC-SS approach and its extension to the initiation of gonadotropin therapy results in considerable reduction of the time to ovulation, and favorable ovulation rates and reproductive outcome. Large-scale confirmation of these findings by properly designed randomized controlled trials may lead to a change of practice in the treatment of anovulatory infertility in PCOS patients, allowing simplification of treatment and a shorter time to ovulation and pregnancy.

Placental histopathology in IVF pregnancies resulting from the transfer of frozen-thawed embryos compared with fresh embryos.

PURPOSE: To study whether placentas of singleton pregnancies conceived after fresh embryo transfer (ET) contain more histopathological lesions compared with placentas of singleton pregnancies conceived after frozen-thawed embryo transfer (FET). METHODS: A prospective cohort study of placental histopathology in 131 women with singleton IVF pregnancies who delivered at a single medical center, between December 2017 and May 2019. The prevalence of different placental histopathology lesions was compared between women who conceived after fresh ET and FET. RESULTS: Women who conceived after fresh ET (n = 74) did not differ from women who conceived after FET (n = 57) with regard to maternal age, BMI, nulliparity, or infertility diagnosis. Gestational week at delivery was lower in pregnancies conceived after fresh ET (38.5 vs. 39.2 weeks, respectively, p = 0.04), and a trend for a lower birthweight following fresh ET was noted (3040 vs. 3216 g, respectively, p = 0.053). However, placental histopathology analysis from pregnancies conceived after fresh ET was comparable to pregnancies conceived after FET, with regard to the prevalence of maternal vascular malperfusion lesions (45.9% vs. 50.9%, respectively, p = 0.57), fetal vascular malperfusion lesions (17.6% vs. 21.1, p = 0.61), acute inflammatory response lesions (28.4% vs. 28.1%, respectively, p = 0.96), and chronic inflammatory response lesions (13.5% vs. 8.8%, respectively, p = 0.48). CONCLUSION: Placental histopathology did not differ between IVF pregnancies conceived after fresh and frozen ET. These results are reassuring for clinicians and patients who wish to pursue with transferring fresh embryos.

Ovarian stimulation for freeze-all IVF cycles: a systematic review.

BACKGROUND: Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established. OBJECTIVE AND RATIONALE: We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles. SEARCH METHODS: A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018. OUTCOMES: Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2-3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles. WIDER IMPLICATIONS: Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.

Modified natural-cycle cryopreserved embryo transfer: is a washout period needed after a failed fresh cycle?

RESEARCH QUESTION: Are the characteristics of the natural cycle or modified natural cycle (mNC), or live birth rates (LBR), affected by delaying frozen embryo transfer (FET) after a failed fresh IVF cycle? DESIGN: In a retrospective study, conducted at a university-affiliated tertiary centre, 198 women aged 18-45 years undergoing their first FET cycle after a failed fresh embryo transfer attempt using an mNC were evaluated. Cycles were divided according to the time interval between oocyte retrieval and the start of the FET cycle into the immediate FET group (<22 days) and the delayed FET group (≥22 days). The main outcome measures were ovulation day and LBR. RESULTS: The mean interval between oocyte retrieval and the start of the FET cycle was 15.6 ± 3.2 days in the immediate FET group and 84.8 ± 73.7 days in the delayed FET group (P < 0.001). Ovulation day was significantly delayed in the immediate FET group (day 17.1 ± 4.4 versus day 15.4 ± 3.7; P = 0.004). There was no difference between the immediate and delayed FET groups in terms of clinical pregnancy rate (CPR) (25.4% and 25.0%, respectively) or LBR (21.2% and 20.0%, respectively). CONCLUSIONS: Natural-cycle characteristics are similar in immediate and delayed cycles, except for a slight delay in ovulation day. Deferring mNC-FET after a failed fresh IVF cycle does not improve the reproductive outcome. These results should encourage patients and clinicians who want to proceed with FET immediately after failure of fresh IVF.

Screening for blood born viruses in assisted reproduction: is annual testing necessary?

PURPOSE: Screening for blood born viruses is routinely performed before fertility treatment in assisted reproduction technology (ART) clinics worldwide. It involves testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), among others. Identifying patients with positive viral screening allows to refer them and their partners for appropriate counseling and treatment. The need for repeat viral screening and its required frequency have never been clearly established. In Israel, viral screening is mandatory and is repeated annually. Our aim was to determine the prevalence of HBV, HCV, and HIV seroconversion in patients with negative screening upon initiation of ART treatment. METHODS: A retrospective analysis of viral screening tests of all fertility patients in a single assisted conception unit between 1997 and 2015. RESULTS: During the study period, 2844 patients were treated at our clinic, out of whom 1945 patients met the inclusion criteria. The average length of treatment was 1.61 ± 0.81 years, during which female patients underwent screening tests 2.6 ± 0.9 times, and male patients 2.3 ± 1.2 times. No case of seroconversion to any of the three viruses was noted during the entire study period, resulting a seroconversion rate of 0%. CONCLUSIONS: Primary infection with HBV, HCV, or HIV is an extremely rare event among Israeli infertile patients, and the risk for seroconversion in this population is practically nil. Annual screening of both partners leads to substantial costs and appears to be futile. Our results question the current practice and support increasing the interval between screening tests in low-risk populations.