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).

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.

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.

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.

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.

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.

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.

"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.

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.

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.

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.

The association between level of physical activity and pregnancy rate after embryo transfer: a prospective study.

RESEARCH QUESTION: Is physical activity after embryo transfer, as assessed by a smart band activity tracker, associated with decreased pregnancy rates? DESIGN: Prospective observational cohort study comprising infertile women aged < 38 years, who had undergone fewer than three previous embryo transfers, achieved a good ovarian response and were undergoing frozen-thawed embryo transfer in a tertiary-referral centre. A validated smart band activity tracker was used to assess physical activity level immediately after the embryo transfer and until the pregnancy test. No specific recommendations were given to participants on level or intensity of physical activity. Physicians and patients were blinded to the data stored in the pedometer. Primary outcome was ongoing pregnancy rate. RESULTS: Fifty women met the inclusion criteria. Ongoing pregnancy rate was 30%. In a pooled analysis, participants walked significantly fewer steps per day on the day of embryo transfer compared with the first 2 days after embryo transfer (4075, interquatile range [IQR] 2932-5592 versus 5204, IQR4203-8584, P = 0.01). No significant difference was observed between pregnant women and non-pregnant women in the median steps per day after embryo transfer until serum beta-HCG was measured (7569, IQR 6008-10884 versus 6572.5, IQR 5299-8786, P = 0.43). No significant difference was observed in the median number of steps on the day of embryo transfer or the first 2 days after embryo transfer between pregnant and non-pregnant women. CONCLUSIONS: A quantitative objective assessment of the association between physical activity and pregnancy rates after frozen-thawed embryo transfer was conducted. Ambulation after embryo transfer has no adverse effect on pregnancy rates and, therefore, women should resume regular activity immediately after embryo transfer.

Obstetric, neonatal and child development outcomes following assisted hatching treatment: a retrospective cohort study.

Assisted hatching (AH) involves artificial disruption of the zona pellucida prior to embryo transfer. The purpose of this study is to examine the safety of AH technique and its effect on obstetrical, perinatal and neonatal outcomes and risk of developmental delay. This is a retrospective cohort of ART cycles using laser AH technique. The study group consisted of 120 cases of AH cycles resulting in singleton pregnancies and live births compared with 113 control cases. A current phone questionnaire was conducted to assess child development in the first year of life. AH was not associated with increased risk for all obstetrical and perinatal outcomes examined including PPROM, gestational diabetes, hypertensive diseases of pregnancy, delivery by cesarean section, gestational age at delivery, low birth weight (LBW), preterm birth and neonatal Apgar score (p>.05). No significant differences were observed between AH and control group in rates and risk of congenital malformations (5.8 vs. 4.4%, respectively, OR 1.33, 95% CI 0.41-4.34) and developmental delay (19.2 vs. 12.8%, respectively, OR 1.62, 95% CI 0.74-3.52). AH did not increase the risk of obstetrical and neonatal complications in singleton pregnancies, including congenital malformations and child developmental delay. AH may therefore be considered a safe method of ART.

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).

A Novel Stimulation Protocol for Poor-Responder Patients: Combining the Stop GnRH-ag Protocol with Letrozole Priming and Multiple-Dose GnRH-ant: A Proof of Concept.

OBJECTIVE: The objective of this study was to examine whether the combined Stop GnRH-agonist (GnRH-ag), letrozole priming, and multiple-dose GnRH-antagonist (GnRH-ant) protocol may improve in vitro fertilization/intracytoplasmic sperm injection cycle in poor ovarian responders (PORs). DESIGN: This was a historical cohort, proof of concept study under tertiary setting at University affiliated Medical Center. PATIENTS: Five PORs fulfilling the POSEIDON Group 4 criteria were included. MAIN OUTCOME MEASURES: Number of oocytes retrieved, number of top-quality embryos (TQEs), and controlled ovarian hyperstimulation (COH) variables were the main outcome measures. RESULTS: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol revealed significantly higher number of follicles >13 mm on the day of hCG administration and higher number of oocytes retrieved, with non-significantly more TQEs and a reasonable clinical pregnancy rate. CONCLUSIONS: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol is a valuable tool in the armamentarium for treating POSEIDON Group 4 patients. Further large prospective studies are needed to elucidate its role in POR and to identify the specific characteristics of women (before initiating ovarian stimulation) that will aid both fertility specialists' counseling and their patients in adjusting the appropriate COH protocol.

Does the number of embryos loaded on a single cryo-carrier affect post-vitrification survival rate?

BACKGROUND: We aimed to assess whether the survival rate of embryos is influenced by the number of embryos/oocytes loaded on a single cryo-carrier during vitrification. METHODS: This was a retrospective study that included 974 patients who underwent thawing of 1896 embryo-warming cycles between September 2016 and January 2020. A distinct analysis was made for cleavage stage embryos (2-10-cell stage) and blastocysts. For vitrification, embryos were placed in a Cryotop™ open device using a SAGE vitrification kit following the manufacturer's instructions. Warming was carried using a SAGE warming vitrification kit according the manufacturer's instructions. RESULTS: Total post-vitrification survival rates of embryos at the cleavage stage or blastocyst stage was 94.8%. At the cleavage stage, cryo-preserving three embryos per single cryo-carrier gave the highest full intact embryo survival rate (91.5%) compared with one or two embryo(s) per single cryo-carrier (85.7%, P < 0.0002 and 87.3%, P < 0.004). Conversely, post warmed full intact blastocyst survival rate for two blastocysts was significantly lower compared with one blastocyst (76.7% vs. 87.9%, P < 0.0193) per single cryo-carrier. CONCLUSION: Post-thawing survival rate following vitrification is affected by the number of embryos per single cryo-carrier undergoing the vitrification equilibration phase, with the optimum number of three cleaved embryos or one blastocyst per single cryo-carrier. Further studies are required to determine the optimum number of cleaved embryos or blastocysts that should be loaded onto a single cryo-carrier vitrification device.

Does gonadotropin-releasing hormone agonist cause luteolysis by inducing apoptosis of the human granulosa-luteal cells?

OBJECTIVES: To evaluates the effect of different modes of final follicular maturation triggering on the degree of apoptosis of granulosa cells (GCs) and the potential effect on progesterone secretion. METHODS: Thirty patients undergoing controlled ovarian hyperstimulation for IVF who received hCG, GnRH agonist, or dual trigger for final follicular maturation were included in the study. Granulosa cells were obtained at the time of oocyte retrieval. The proportion of apoptotic cells was evaluated via TUNEL and immunohistochemistry. RESULTS: The proportion of apoptotic cells was significantly higher in the GnRH agonist-alone group compared to hCG-alone and the dual trigger groups (13.5 ± 1.5% vs. 7.8% ± 1.8 vs. 10.1% ± 2, respectively, P < 0.01). Moreover, the expression of active-caspase-3 was also significantly increased in the GnRH agonist-alone group compared with the hCG-alone and the dual trigger groups (15.5% ± 2.9 vs. 8.4% ± 1.6 vs. 12.7% ± 2.6, respectively, P < 0.01). The progesterone levels measured in the granulosa-luteal cell culture medium after 24 h of incubation were similar between the three groups. CONCLUSIONS: The levels of apoptosis are increased after GnRH agonist/dual trigger. The increased apoptosis might be one of the culprit of the subsequent premature demise of the corpus luteum post GnRH agonist trigger.