The association of endometrial closure during cesarean section to the risk of developing uterine scar defect: a randomized control trial.

PURPOSE: The surgical technique for uterine closure following cesarean section influences the healing of the cesarean scar; however, there is still no consensus on the optimal technique regarding the closure of the endometrium layer. The aim of this study was to compare the effect of closure versus non-closure of the endometrium during cesarean section on the risk to develop uterine scar defect and associated symptoms. METHODS: A randomized prospective study was conducted of women undergoing first elective cesarean section at a single tertiary medical center. Exclusion criteria included previous uterine scar, preterm delivery and dysmorphic uterus. Women were randomized for endometrial layer closure versus non-closure. Six months following surgery, women were invited to the ambulatory gynecological clinic for follow-up visit. 2-D transvaginal ultrasound examination was performed to evaluate the cesarean scar characteristics. In addition, women were evaluated for symptoms that might be associated with uterine scar defect. Primary outcome was defined as the residual myometrial thickness (RMT) at the uterine cesarean scar. Data are presented as median and interquartile range. RESULTS: 130 women were recruited to the study, of them follow-up was achieved in 113 (86.9%). 61 (54%) vs. 52 (46%) of the women were included in the endometrial closure vs. non-closure groups, respectively. Groups were comparable for patient's demographic, clinical characteristics and follow-up time for postoperative evaluation. Median RMT was 5.3 (3.0-7.7) vs. 4.6 (3.0-6.5) mm for the endometrial closure and non-closure groups, respectively (p = 0.38). Substantially low RMT (< 2.5 mm) was measured in four (6.6%) women in the endometrial closure group and three (5.8%) of the women in the non-closure group (p = 0.86). All other uterine scar sonographic measurements, as well as dysmenorrhea, pelvic pain and intermenstrual bleeding rates were comparable between the groups. CONCLUSION: Closure versus non-closure of the endometrial layer during cesarean uterine incision repair has no significant difference in cesarean scar characteristics and symptom rates at 6 months follow-up.

The association between uterine scar defect (niche) and the presence of symptoms.

RESEARCH QUESTION: Is there association between the presence of a uterine niche and the presence of symptoms? DESIGN: This cross-sectional study was conducted at a single tertiary medical centre. All women who underwent Caesarean section from January 2017 to June 2020 were invited to the gynaecological clinics, and requested to complete a questionnaire regarding symptoms related to the presence of a niche (heavy menstrual bleeding, intermenstrual spotting, pelvic pain, infertility). Transvaginal two-dimensional ultrasonography was performed to assess the uterus and uterine scar characteristics. The primary outcome was defined as the presence of a uterine niche, evaluated by length, depth, residual myometrial thickness (RMT) and ratio between the residual myometrial thickness (RMT) and adjacent myometrial thickness (AMT). RESULTS: Of 524 women who were eligible and scheduled for evaluation, 282 (54%) completed the follow-up; 173 (61.3%) were symptomatic and 109 (38.6%) asymptomatic. Niche measurements, including RMT/AMT ratio, were comparable between the groups. In a sub-analysis of each symptom, heavy menstrual bleeding and intermenstrual spotting were associated with reduced RMT (P = 0.02 and P = 0.04, respectively) compared with women with normal menstrual bleeding. An RMT less than 2.5 mm was significantly more prevalent in women reporting heavy menstrual bleeding (11 [25.6%] versus 27 [11.3%]; P = 0.01] and new infertility (7 [16.3%] versus 6 [2.5%]; P = 0.001]. In logistic regression analysis, infertility was the only symptom associated with an RMT less than 2.5 mm (B = 1.9; P = 0.002). CONCLUSIONS: A reduced RMT was found to be associated with heavy menstrual bleeding and intermenstrual spotting, while values below 2.5 mm were also associated with infertility.

The effects of Covid-19 mRNA vaccine on adolescence gynecological well-being.

KEY MESSAGE: Menstruation of adolescent girls might be influenced by Covid-19 mRNA vaccine, however, the ovarian reserve estimated by AMH is not compromised. BACKGROUND: Recent studies have suggested that the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine causes menstrual abnormalities which led to concerns regarding its influence on the reproductive system. This study aims to investigate the influence of the SARS-CoV-2 mRNA vaccine on gynecologic well-being and future fertility of adolescent girls. METHODS: This is a prospective cohort study conducted at a university affiliated medical center between June and July 2021. Adolescent girls aged 12-16 years who were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart) were included in the study. All participants completed a computerized questionnaire regarding their general medical and gynecological background at recruitment and 3 months later. Blood samples were collected for AMH levels before and 3 months following the first mRNA vaccine RESULTS: The study group consisted of 35 girls, and of them, follow-up was completed by questionnaire and AMH sampling in 35 (90%) and 22 (56%) girls, respectively. Among the 22/35 girls who reported regular menstruation before vaccination, seven (31.8%) experienced irregularities post-vaccination. Four of the eight pre-menarche girls included in the study reported on menarche on follow-up. Median AMH levels were 3.09 (IQR 1.96-4.82) µg/L and 2.96 (2.21-4.73) µg/L at baseline and after 3 months, respectively (p = 0.07). After controlling for age, BMI and presentation of side effects, no association was demonstrated to the change in AMH levels (AMH2-AMH1). CONCLUSIONS: Although menstruation of adolescent girls might be influenced by Covid-19 mRNA vaccine, it seems that the ovarian reserve estimated by AMH is not compromised. CLINICAL TRIAL REGISTRATION: National Institutes of Health (NCT04748172).

Fertility and pregnancy complications following chorioamnionitis.

Acute chorioamnionitis complicates 1-2% of all pregnancies and might increase the prevalence of endometritis that can cause Asherman syndrome or adhesions, but little is known about the direct effects of chorioamnionitis on future fertility. We aimed to evaluate the effect of chorioamnionitis on future fertility and obstetrics complications in patients diagnosed with chorioamnionitis during their pregnancy. We performed an observational, case-control retrospective study of pregnant women aged 18-40 years old, hospitalized with a diagnosis of chorioamnionitis between January 2013 and December 2017. The control group consisted of patients with similar demographic/obstetrics characteristics, matched with a ratio of 1:2 without chorioamnionitis. The prevalence of post gestational diagnostic hysteroscopy was significantly higher in the study group as compared to the control group (22.9% versus 9.0%, respectively; p = 0.005). Moreover, the study group underwent significantly more operative hysteroscopy compared to the control group (10.8% versus 3.6%, respectively; p = 0.04). The patients in the study group had significantly higher prevalence of miscarriages (27% versus 13.2%, respectively; p < 0.01). We conclude that chorioamnionitis may cause endometritis with the consequent impaired fertility, necessitating comprehensive evaluations for secondary infertility, including hysteroscopy aiming to treat intrauterine adhesions that may affect and impair fertility.

Elective egg freezing patients may benefit from increasing the maximal daily gonadotropin dose above 300IU.

OBJECTIVE: Nowadays, patients attempting social/elective egg freezing has spread globally. Ovarian stimulation (OS) with high daily gonatotropin doses, are commonly offered to this group of patients, aiming to achieve the maximal oocytes cohort with minimum IVF cycle attempts. We aim to assess the IVF-ET outcome, and specifically the oocyte yield, of patients undergoing two successive IVF cycle attempts for elective egg freezing (EEF), and whether changing the daily gonadotropin dose in the second IVF cycle attempt, affect the outcome. PATIENTS AND METHODS: All women admitted to our IVF unit for social/EEF, who underwent 2 consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300 IU were included. Ovarian stimulation characteristics, duration of OS, number of retrieved oocytes, number of mature oocytes were assessed and compared between the 1st and the 2nd IVF cycle attempts, and between the different daily gonadotropin doses and the oocyte yields in the 2nd cycle attempt (increase, decrease or no change). MAIN OUTCOME MEASURES: Oocytes and mature oocytes yield in the 2nd as compared to the 1st IVF cycle attempt. RESULTS: A reduced oocyte yield in the 2nd cycle attempt was observed in those who highly responded in the 1st attempt, regardless the daily dose in the 2nd cycle attempt (whether it was increased, no change and decreased). Moreover, the proportion of patients with same or more oocytes in the 2nd IVF cycle attempt was significantly lower in patients with high peak E2 levels, compared to those with peak E2 levels < 9175 pmol/L. Among patients with high peak E2 (> 9175 pmol/L), those who achieved a lower oocytes yield in the 2nd IVF cycle attempt had lower basal Day-3 FSH/LH ratio (1.5 + 0.5 vs 1.8 + 0.8, p < 0.03) and higher oocyte (range: 7-28, median:10; vs range: 2-15, median:7) and mature oocytes yields. With a cut-off of 9 oocytes, 78.8% of those with > 9 oocytes and 61.8% of those with < 9 oocytes will achieve lower/higher oocytes yield in the 2nd IVF cycle attempt, respectively. CONCLUSIONS: Ovarian stimulation with high daily gonatotropin doses (300 IU) should be offered to patients attempting social/EEF. Moreover, in their 2nd IVF cycle attempt, those with high peak E2 (> 9175 pmol/L) in the 1st attempt, and basal Day-3 FSH/LH ratio < 1.5 and/or more than 9 oocytes retrieved, should receive same OS protocol with no change in the daily gonadotropin dose.

Observations on clinical assessment of endometrial receptivity.

This brief review will examine the investigation of the endometrial cavity before embryo transfer using various techniques, including hysteroscopy, endometrial biopsy using immunohistochemistry and molecular microarray, and ultrasound imaging. All these investigative tools are presently subject to controversy and require large prospective controlled trials for validation. During embryo transfer, the occurrence of a retained embryo does not appear to have a negative impact on pregnancy outcome, and finally, consistent data indicate that physical activity immediately after embryo transfer has no impact on pregnancy outcome.

The in-vitro effect of gonadotropins' type and combination on Granulosa cells gene expressions.

OBJECTIVE: Nowadays, different modes and timing of GnRH-agonist combined with hCG trigger, for final follicular maturation, have been described. While LH + FSH are the naturally occurring final follicular maturation trigger, hCG is commonly use during stimulated cycle, and recently the introduction of the Dual/Double trigger combines LH + FSH + hCG. In the present study we aim to investigate the messenger RNA (mRNA) expression of reproduction-related genes in human granulosa cells (GCs) exposed to the aforementioned different types and combinations of gonadotropins. MATERIAL AND METHODS: Mural GCs were obtained from follicular fluid aspirated during IVF protocol. GCs were seeded in culture for 4 days with daily medium exchange followed by administration of either hCG (1 U/ml); FSH (1 U/ml) and LH (8 U/ml); or hCG (1 U/ml) and FSH (1 U/ml) and LH (8 U/ml) for 16 h. mRNA was purified from harvested GCs and gene expression was quantitative by qPCR. MAIN OUTCOME MEASURES: The expression of genes related to steroidogenesis (StAR/ CYP19) and oocyte maturation (COX2/Amphiregulin) in cultured GCs. RESULTS: The Dual/Double trigger (LH + FSH + hCG) showed higher activation of steroidogenesis (StAR/CYP19) and maturation (COX2/Amphiregulin) as compared to the naturally occurring trigger (LH + FSH) and the hCG triggers. Moreover, while the naturally occurring trigger (LH + FSH) activated maturation significantly and more intensely than the hCG trigger, no in between group differences were observed with regards to steroidogenic related genes. CONCLUSIONS: Our findings are in agreement with clinical experience, demonstrating the superiority of the double/dual (LH + FSH + hCG) trigger over the naturally occurring and the hCG triggers.

Predicting IVF outcome in poor ovarian responders.

BACKGROUND: Poor responders to ovarian stimulation are one of the most challenging populations to treat. As a failed cycle can cause a considerable emotional and economical loss, adequate fertility counseling addressing patients' expectations are highly important when facing patients with poor ovarian response. The study aimed to evaluate reproductive outcomes and to identify factors associated with live birth (LB) after fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles of patients fulfilling the Bologna criteria for poor ovarian response (POR). METHODS: A retrospective study included 751 IVF/ICSI treatment cycles which yielded up to three retrieved oocytes, at a tertiary referral hospital between January 2016 and February 2020. A logistic regression analysis was used to adjust for confounders. RESULTS: Clinical pregnancy and LB rate per cycle were significantly higher among women younger versus older than 40 years (9.8% and 6.8% vs 4.5% and 2.1%, p < 0.01, respectively). Patients who achieved LB were significantly younger, had higher number of oocytes retrieved, fertilization rate and top-quality embryos (p < 0.05). Multivariable regression analysis identified patient's age (OR 0.90; 95% CI 0.845-0.97; p = 0.005) and mean number retrieved oocytes (OR 1.95; 95% CI 1.20-3.16; p = 0.007) as factors significantly associated with the probability of a LB. CONCLUSIONS: The woman's age and the number of retrieved oocytes are both independent predicting factors of live birth in poor ovarian responders. Considering the risks, the high financial investment and poor reproductive outcomes involved in IVF treatments, raises questions regarding the adequacy of providing treatments in these patients' population. POR younger than 40 years may represent a possible exception due to acceptable probability for a LB.

Embryos derived from delayed mature oocyte should be cryopreserved and are favourable to transfer in a following endometrium synchronize frozen-thawed cycle.

Oocytes eligible for intracytoplasmic sperm injection (ICSI) are those that have progressed through meiosis to metaphase 2 (MII). The remaining delayed mature oocytes can be injected, aiming to achieve more embryos and a better chance to conceive. We aimed to assess the outcome of delayed matured oocytes, derived from either germinal vesicles or metaphase 1 (MI), that reached maturity (MII) 24 h following retrieval. The study population consisted of 362 women who underwent 476 IVF cycles. While fertilization rates were comparable between the sibling delayed mature oocyte group compared with injection on day 0 group (58.4% vs 62%, respectively, P = 0.07), the top-quality embryo rate per injected MII day 0 oocyte was significantly higher compared with day 1 injected oocyte (57.5% vs 43.9% respectively, P < 0.001). Moreover, following fresh transfer of embryos derived from delayed mature oocytes, implantation rate and the clinical pregnancy (CPR) and live-birth rates (LBR) per transfer were 3.9%, 3.3% and 1.6% respectively. When considering the following thawed embryo transfer cycles, implantation, pregnancy and LBR were non-significantly higher (10%, 8.3% and 8.3%, respectively). Although clinical outcomes are significantly lower when using embryos derived from delayed mature oocyte to mature day 0 oocytes, the additional embryos derived from delayed mature oocytes might contribute to the embryo cohort and increase the cumulative live-birth rate per retrieval. Moreover, the embryos derived from delayed mature oocyte favour a transfer in a frozen-thawed cycle rather than in a fresh cycle.

Predictive value of new onset versus primary meconium-stained amniotic fluid.

BACKGROUND: Transition of clear amniotic fluid to meconium-stained fluid is a relatively common occurrence during labor. However, data regarding the clinical significance and the prognostic value of the presence of meconium-stained amnionic fluid (MSAF) are scarce. This study aimed to investigate delivery and neonatal outcomes according to the presence of MSAF and the timing of the meconium passage. METHODS: We used an historical cohort study at a single tertiary medical center in Israel between the years 2011 and 2018. Women were divided into two groups according to timing of meconium passage: primary MSAF (MSAF present at membrane rupture) and secondary MSAF (clear amnionic fluid that transitioned to MSAF during labor). Neonatal complication rates were compared between groups. Composite adverse neonatal outcome was defined as arterial cord blood pH <7.1, 5 min Apgar score ≤7, and/or neonatal intensive care unit admission. RESULTS: The study cohort included 56 863 singleton term births. Of these, 9043 (15.9%) were to women who had primary MSAF, and 1484 (2.6%) to those with secondary MSAF. Secondary MSAF compared with primary MSAF increased the risks of cesarean birth and operative vaginal delivery, increased the risks of low one- and five-minute Apgar scores and low arterial cord blood pH, and increased hospital stay duration. Multivariate analysis revealed that secondary MSAF was independently associated with an increased risk of composite adverse neonatal outcome (OR1.68, 95% CI 1.25-2.24, p < 0.001) compared with primary MSAF. CONCLUSIONS: In this sample, secondary MSAF was associated with more adverse neonatal outcomes than primary MSAF. Closer monitoring of fetal well-being may be prudent in these cases.

The effect of coronavirus disease 2019 immunity on frozen-thawed embryo transfer cycles outcome.

OBJECTIVE: To study the effect of patients' immunization after coronavirus disease 2019 (COVID-19) infection or messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine on frozen-thawed embryo transfer (FET). DESIGN: Cohort retrospective study. SETTING: Tertiary university affiliated medical center. PATIENT(S): All consecutive patients undergoing FET cycles in our center. The study group (immune group) consisted of patients treated during the COVID-19 pandemic (between January 2021 and August 2021) who either recovered from COVID-19 infection or received the mRNA SARS-CoV-2 vaccine. The control groups consisted of patients treated during the COVID-19 pandemic (between January 2021 and August 2021) but were not infected or did not receive the mRNA SARS-CoV-2 vaccine (not-immune2021 group) and those treated between January 2019 and August 2019 (before the pandemic) (not-immune2019 group). INTERVENTION(S): Frozen-thawed embryo transfer cycles. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rates and FET cycles' characteristics. Data on patient age and variables related to infertility treatment were collected from the patient records. RESULT(S): During the study periods, 428 patients underwent 672 FET cycles. The immune group consisted of 141 patients who underwent 264 FET cycles (44 in postinfection and 220 in postvaccination), whereas the not-immune2021 and not-immune2019 groups consisted of 93 and 194 patients undergoing 125 and 283 FET cycles, respectively. Patients' characteristics and the types of endometrial preparations were comparable between the study groups. The implantation rate and clinical and ongoing pregnancy rates per transfer were similar between the study groups (immune group, postinfection and postvaccination; not-immune2021 group; not-immune2019 group). CONCLUSION(S): Coronavirus disease 2019 infection or vaccination did not affect patients' performance or implantation in their subsequent FET cycle.

"One-stop shop" for the evaluation of the infertile patient: hystero-salpingo foam sonography combined with two and three dimensional ultrasound and sonohysterography.

Hysterosalpingo-foam sonography (HyFoSy) is considered an acceptable alternative for hysterosalpingography (HSG). By combining HyFoSy with two and three-dimensional (2D and 3D) ultrasound and hysterosonography, a complete fertility work-up can be done. We aimed to evaluate the value of a combined ultrasound examination for fertility work-up. During the study period 113 women were examined. Five of 113 (4.4%) examinations were abandoned due to intra-uterine adhesions that were detected by hysterosonography, and five (4.4%) were abandoned due to technical difficulties. Of 103 women who had completed the examination, 2D ultrasound revealed six patients with hydrosalpinx (5.8%) and sonographic signs of adenomyosis in 13 (12.6%) patients. By combining 2D ultrasound with hysterosonography, two (1.9%) fibroids that were penetrating the uterine cavity and seven (6.8%) endometrial polyps were detected. HyFoSy showed bilateral patent tubes in 58 patients (56.3%), unilateral tubal occlusion in 29 (28.1%) and bilateral tubal occlusion in 16 (15.5%). This study shows that the 'one-stop shop' examination is feasible. The combined examination had detected 16 pathological findings that would have not been detected by HyFoSy alone. Hence, it should be offered to couples undergoing routine infertility work-up.IMPACT STATEMENTWhat is already known on this subject? The accuracy of the HyFoSy alone has been evaluated in different studies, but this presented ultrasound scan is integrating 4 different modalities in one exam (2D scanning of the pelvis, 3D scanning of the uterus, hysterosonography and HyFoSy) and we were able to evaluate the female pelvic organs, including the uterine cavity, the tubes and the ovaries, in order to expand the range of diagnosed pathologies.What do the results of this study add? The concept of 'one-stop shop' for the evaluation of female pelvis in couples suffering from infertility is feasible, has comparable accuracy as HSG for tubal occlusion, and higher detection rate for uterine malformations.What are the implications of these findings for clinical practice and/or further research? We suggest to incorporate this examination in routine fertility work-up.

The Influence of Cesarean Delivery on Ovarian Reserve: a Prospective Cohort Study.

To assess the association between cesarean delivery and ovarian reserve, as compared to vaginal delivery. A prospective case control study conducted at a single tertiary medical center between June 2018 and June 2019. Study population included women with singleton pregnancy that underwent first cesarean delivery that were compared to women undergoing normal vaginal delivery. Women with low ovarian reserve, endometriosis, previous pelvic surgery, chronic maternal disease, and active labor were excluded. Ovarian reserve was estimated by Anti-Mullerian hormone (AMH) levels that was determined twice for each participant: up to a week before and 3 months after delivery. Primary outcome was defined as the delta in AMH levels. Data were analyzed by non-parametric tests. During the study period, 135 women were enrolled, of them 63 (47%) underwent cesarean delivery and 72 (53%) had vaginal delivery. Women in the cesarean delivery group were older (34 (31-38) vs. 32 (29-35); p = 0.001); nevertheless, AMH levels measured before delivery were comparable between the two groups (0.92 (0.51-1.79) vs. 0.95 (0.51-1.79) pg/mL; p = 0.42). AMH levels measured after delivery were more than doubled in the study and control groups (2.15 (1.24-3.05) vs. 2.62 (1.05-5.09); p = 0.50), and delta AMH levels were also found comparable (1.25 (0.61-2.22) vs. 1.59 (0.63-3.41), respectively; p = 0.43). Linear regression analysis including age, mode of delivery, gestational age at delivery, and delta hemoglobin levels revealed that only maternal age was significantly associated with delta in AMH levels (B = - 0.09, p = 0.04). Cesarean delivery does not decrease ovarian reserve as estimated by AMH.

Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

RESEARCH QUESTION: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? DESIGN: A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. RESULTS: The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 â€¯×  106/ml, with only a single participant (1.3%) with a sperm count of 12.5 â€¯×  106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. CONCLUSIONS: The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Cancer diagnosis among women with recurrent pregnancy loss: a retrospective cohort study.

RESEARCH QUESTION: What is relationship between unexplained recurrent pregnancy loss (RPL) and risk of cancer morbidity? DESIGN: A retrospective observational cohort study was conducted, based on data from a tertiary medical centre. RPL cases (exposed) were defined as women presenting with three or more unexplained confirmed pregnancy losses at 5-24 weeks, whose first visit to the RPL clinic was between 1990 and 2010. The unexposed group included women giving birth who were not RPL patients; these were matched by age and year of giving birth/admission (1:5 ratio). Data from the RPL and the live birth registries were cross-linked to the Israeli national cancer registry according to the unique ID number and merged into one database. RESULTS: The study group comprised 937 RPL patients who were matched by maternal age (P = 1.0) and admission date (P = 0.84) to 4685 women achieving a live birth. There was no difference in overall cancer incidence between groups (adjusted odds ratio [OR] 0.76, 95% confidence interval [CI] 0.55-1.03; P = 0.08). The secondary RPL group showed a trend towards decreased cancer morbidity incidence compared with primary RPL (adjusted OR 0.65, 95% CI 0.41-1.03; P = 0.07). Analysis by cancer type showed a similar risk for breast cancer among women with RPL compared with live birth, but a significantly lower risk for gynaecological cancers among women with RPL (adjusted OR 0.25, 95% CI 0.08-0.79; P = 0.018). CONCLUSIONS: Unexplained RPL may be related to a lower risk of gynaecological cancers, possibly explained by hyper-responsive immunological mechanisms involving uterine natural killer cells.

GnRH-Agonist Ovulation Trigger in Patients Undergoing Controlled Ovarian Hyperstimulation for IVF with Stop GnRH-Agonist Combined with Multidose GnRH-Antagonist Protocol.

OBJECTIVE: This study aimed to characterize those patients undergoing the stop gonadotropin-releasing hormone (GnRH)-agonist combined with multidose GnRH-antagonist protocol, with suboptimal response to GnRH-agonist trigger in in vitro fertilization (IVF) cycles. DESIGN: This is a cohort study. SETTING: The study was conducted in a university hospital. PATIENTS: All consecutive women admitted to our IVF unit from February 2020 through November 2020 who reached the ovum pick-up stage were reviewed. INTERVENTIONS: Triggering final oocyte maturation by GnRH-ag alone (GnRH-ag trigger group), or combined with hCG (dual trigger group), in patients undergoing the stop GnRH-agonist combined with multidose GnRH-antagonist protocol was performed. MAIN OUTCOME MEASURE: The main outcome measure was LH level 12 h after the trigger. RESULTS: Five out of the 32 patients (15.6%) demonstrated suboptimal response as reflected by LH levels <15 IU/L 12 h after GnRH-agonist trigger. Moreover, while no differences were observed in oocyte recovery rate, maturity, or embryo quality between the different study groups (GnRH-ag trigger and dual trigger groups), those achieving a suboptimal response to the GnRH-agonist trigger (post-trigger LH <15 mIU/mL) demonstrated significantly higher number of follicles and peak estradiol levels at the day of trigger, compared to those with optimal response (post-trigger LH >15 mIU/mL). CONCLUSIONS: The stop GnRH-agonist combined with GnRH-antagonist protocol enables the substitution of hCG with GnRH-ag for final oocyte maturation. However, caution should be taken in high responders, where the dual trigger with small doses of hCG (1,000-1,500 IU) should be considered, aiming to avoid suboptimal response (post-trigger LH levels <15 IU/L).

How far is too far? Does time interval between GnRH antagonist and GnRH agonist trigger in GnRH antagonist cycles matter?

RESEARCH QUESTION: What is a suitable time interval between the last GnRH antagonist exposure and GnRH agonist (GnRHa) triggering for final follicular maturation? DESIGN: A retrospective cohort study including 413 patients undergoing GnRH antagonist cycles in which GnRHa trigger was used, either solely or as a dual trigger. The primary outcome measure was the follicle/mature oocyte ratio. Cycles were analysed according to the time interval between the last GnRH antagonist exposure and the GnRHa triggering: Group 1 included patients with a 12-14 h interval; Group 2: 7-10 h interval; Group 3: 5-6 h interval and Group 4: 2-4 h interval. LH concentration was measured 11-13 h post-GnRHa injection. RESULTS: Median LH value was 65 IU/l. There was a weak but significant correlation between basal LH and the LH surge (R2 = 0.137, P < 0.001). Although square root LH values differed significantly between study groups (P < 0.001; higher in Groups 2 and 3), the follicle/mature oocyte ratio was not different across the four antagonist-agonist interval groups and no correlation was detected between the post-trigger LH concentration and the follicle/oocyte ratio (R2 = 0.011). In a model integrating age, day 3 FSH concentration, maximal oestradiol and body mass index along with the study groups, none of these factors was significantly related to the follicle/mature oocyte outcome ratio. Insufficient surge (LH < 15 IU/l) occurred in 14 (3.4%) cases. Rates of insufficient LH surge did not differ significantly between the groups (2.4%, 3.2%, 3.4% and 7.1% in Groups 1 to 4, respectively; P = 0.5). CONCLUSIONS: LH concentrations post-GnRHa trigger differ in regard to antagonist-agonist intervals, but the follicle/mature oocyte ratio achieved was not affected.

Cumulative IVF outcomes after retrieval of testicular spermatozoa: should we use immotile spermatozoa for ICSI?

RESEARCH QUESTION: What are the cumulative clinical pregnancy rates (CPR) and live births rates (LBR) in intracytoplasmic sperm injection (ICSI) cycles using testicular motile compared with immotile spermatozoa, obtained from testicular sperm aspiration (TESA) or extraction (TESE)? DESIGN: A retrospective analysis of ICSI cycles using TESA or TESE over a period of 7 years. Cycles were divided into two groups according to the motility of the retrieved spermatozoa: Group A consisted of couples with motile spermatozoa; Group B of couples with immotile spermatozoa. Group B was subdivided into two groups: B1 consisted of couples with motile spermatozoa and B2 with immotile spermatozoa after the addition of pentoxifylline. RESULTS: No differences in CPR and LBR per transfer was found between the study groups after fresh embryo transfer. No pregnancies were achieved by vitrified-warmed embryo transfer in group B2. Fertilization rates decreased when using immotile spermatozoa (64.4%, 56%, 37.9%, for groups A, B1 and B2, respectively, P < 0.001). Top-quality embryo rates were higher in groups A and B1 compared with B2 (40.7% and 40.1% versus 19.1%, respectively, P = 0.015). Cumulative CPR (53%, 41.7%, 13.6% for groups A, B1 and B2, respectively, P = 0.005) and LBR (42.4%, 30%, 13.6% for groups A, B1 and B2, respectively P = 0.03) per oocyte retrieval was significantly higher when using motile spermatozoa compared with motile or immotile spermatozoa after adding pentoxifylline. CONCLUSIONS: Although fertilization, top-quality embryo rates, cumulative CPR and LBR decreased when using immotile spermatozoa, ICSI is still valid; therefore, it should be considered and offered to couples before embarking on a donor sperm insemination cycle, or cryopreserving oocytes for future additional testicular sperm retrieval.

Does mRNA SARS-CoV-2 vaccine influence patients' performance during IVF-ET cycle?

OBJECTIVE: No information exists in the literature regarding the effect of mRNA SARS-CoV-2 vaccine on subsequent IVF cycle attempt. We therefore aim to assess the influence of mRNA SARS-CoV-2 vaccine on IVF treatments. DESIGN: An observational study. SETTING: A tertiary, university-affiliated medical center. PATIENTS AND METHODS: All couples undergoing consecutive ovarian stimulation cycles for IVF before and after receiving mRNA SARS-CoV-2 vaccine, and reached the ovum pick-up (OPU) stage. The stimulation characteristics and embryological variables of couples undergoing IVF treatments after receiving mRNA SARS-CoV-2 vaccine were assessed and compared to their IVF cycles prior to vaccination. MAIN OUTCOME MEASURES: Stimulation characteristics and embryological variables. RESULTS: Thirty-six couples resumed IVF treatment 7-85 days after receiving mRNA SARS-CoV-2 vaccine. No in-between cycles differences were observed in ovarian stimulation and embryological variables before and after receiving mRNA SARS-CoV-2 vaccination. CONCLUSIONS: mRNA SARS-CoV-2 vaccine did not affect patients' performance or ovarian reserve in their immediate subsequent IVF cycle. Future larger studies with longer follow-up will be needed to validate our observations.