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Objective To study the effect of patients' immunization following COVID-19 infection or mRNA SARS-CoV-2 vaccine on frozen-thawed embryo transfer (FET). Design A cohort retrospective study Setting Tertiary University Affiliated Medical Center Patients 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 to 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 to August 2021) but were not infected nor received the mRNA SARS-CoV-2 vaccine (not-immune2021 group) and those patients treated between January 2019 to August 2019 (prior to the pandemic) (not-immune2019 group). Intervention FET cycles Main outcome measures Ongoing pregnancy rates and FET cycles' characteristics. Data on patient age and variables related to infertility treatment were collected from the patient records. Results During the study periods, 428 patients underwent 672 FET cycles. The immune group consisted of 141 patients who underwent 264 FET cycles (44 in post-infection and 220 in post-vaccination), while the non-immune2021 and 2019 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. Implantation rate, clinical and ongoing pregnancy rates per transfer were similar between the study groups (immune- group: post-infection and post-vaccination; not-immune2021 group; not-immune2019 group). Conclusions COVID-19 infection or vaccination did not affect patients' performance or implantation in their subsequent FET cycle., In the present study of patients undergoing frozen-thawed embryo transfer (FET) before and during the COVID-19 pandemic, COVID-19 immunity does not affect the immediate subsequent FET cycle outcome.

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), 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 9 oocytes and 61.8% of those with 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

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.

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)?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.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, P0.001). 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.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.

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 p 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.

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.

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.

SummaryOocytes 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.

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 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

Context Gonadotropin-releasing hormone agonist (GnRH-a) serves as an alternative to human chorionic gonadotropin (hCG) to trigger final oocyte maturation, while it significantly reduces the risk of ovarian hyperstimulation syndrome (OHSS), probably by attenuating vascular/endothelial activation. Objectives The objectives of this work are to compare the effect of different modes of final follicular maturation (hCG vs GnRH-a) following ovarian stimulation (OS) for in vitro fertilization (IVF) on endothelial function. Design and Setting A prospective cohort study was conducted at a tertiary medical center. Participants Patients age 37 years or younger, undergoing OS for IVF, were allocated into 2 groups according to the type of final follicle maturation: the hCG group (n = 7) or the GnRH-a group (n = 8). Intervention Endothelial function was assessed by measurement of the peripheral arterial tonometry in reaction to temporary ischemia at 3 study points: day 3 of menstrual cycle (day 0), day of hCG/GnRH-a administration (day trigger) and day of oocyte pick-up (day OPU). The ratio of arterial tonometry readings before and after ischemia is called the reactive hyperemia index (RHI). Decreased RHI ( Main Outcome Measures The main outcomes measures of this study included endothelial function at 3 study points during OS with different modes of triggering final follicular maturation. Results The mean RHI values at day 0 were within the normal range for all patients and comparable between both groups (hCG: 1.7 ± 0.3 vs GnRH-a: 1.79 ± 0.4, P = .6). All patients presented a decrease in RHI values on day trigger, which did not differ between the 2 groups (1.62 ± 0.3 vs 1.4 ± 0.2, respectively, P = .2). However, the hCG group demonstrated a further decrease in RHI on day OPU, whereas patients who received GnRH-a had restored normal endothelial function reflected by increased RHI values (1.4 ± 0.2 vs 1.75 ± 0.2, respectively, P = .03). Conclusions Triggering final follicular maturation with GnRH-a restored normal endothelial function, whereas hCG trigger resulted in a decrease in endothelial function.

OBJECTIVE Our primary objective was to compare maternal and neonatal outcomes based on the attempted mode of extraction. Our secondary objective was to compare the outcomes based on the actual mode of extraction. DESIGN A retrospective cohort study at a single tertiary centre between the years 2011 and 2019. SETTING The study included 1028 cases of term pregnancies in vertex presentation that were delivered by caesarean section at the second stage of delivery. POPULATION Patients were grouped according to the attempted mode of extraction: attempted cephalic extraction (674) and breech extraction (354). A subgroup analysis was conducted, comparing successful cephalic extraction (615), failed cephalic extraction (59) and breech extraction (354). METHODS Both maternal and neonatal complication rates were compared between the groups. RESULTS There were significantly more uterine incision extensions (27.4 versus 11.9%, P

Background Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course. Methods We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed. Results Twenty-four patients were included. Mean patients’ age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p p p p p Conclusion Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders.

Objective To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs). Design An observational cohort study. Setting Single tertiary care medical center. Patient(s) Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post–preimplantation genetic testing for aneuploidy (PGT-A). Intervention(s) Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET. Main Outcome Measure(s) Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET. Result(s) We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact. Conclusion(s) There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant.

Objective Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) activate distinct intracellular signaling cascades. However, due to their similar structure and common receptor, they are used interchangeably during ovarian stimulation (OS). This study aims to assess if the source of LH used during OS affects IVF outcome. Patients and methods This was a cross sectional study of patients who underwent two consecutive IVF cycles, one included recombinant follicular stimulating hormone (FSH) plus recombinant LH [rFSH+rLH, (Pergoveris)] and the other included urinary hCG [highly purified hMG (HP-hMG), (Menopur)]. The OS protocol, except of the LH preparation, was identical in the two IVF cycles. Results The rate of mature oocytes was not different between the treatment cycles (0.9 in the rFSH+rLH vs 0.8 in the HP-hMG, p = 0.07). Nonetheless, the mean number of mature oocytes retrieved in the rFSH+rLH treatment cycles was higher compared to the HP-hMG treatment cycles (10 ± 5.8 vs 8.3 ± 4.6, respectively, P = 0.01). Likewise, the mean number of fertilized oocytes was higher in the rFSH+rLH cycles compared with the HP-hMG cycles (8.5 ± 5.9 vs 6.4 ± 3.6, respectively, p = 0.05). There was no difference between the treatment cycles regarding the number of top-quality embryos, the ratio of top-quality embryos per number of oocytes retrieved or fertilized oocytes or the pregnancy rate. Conclusion The differences in treatment outcome, derived by different LH preparations reflect the distinct physiological role of these molecules. Our findings may assist in tailoring a specific gonadotropin regimen when assembling an OS protocol.

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.

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.

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.

Today, most IVF programs have moved to blastocyst transfer but there is still uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos on day 3. We conducted a retrospective study of 102 patients with one or two cleavage stage embryos that had their embryos transferred on day 3 and 429 patients had their embryos cultured to day 5 for transfer. The number of mature oocytes (4.0 vs 4.6

What is the cumulative incidence of live birth (CILB) for high-order consecutive IVF cycles, and which factors are associated with live birth in women aged ≥41 years using autologous oocytes?A retrospective cohort study including 146 patients aged 41 years to44 years who started their first IVF cycle attempt using autologous oocytes, between January 2006 and December 2013.After 13 IVF cycles, CILB reached up to 33.6%. After six IVF cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth). Mean live birth rate per cycle declined with age at the initial cycle (8% at 41 years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson regression models identified patient's age (RR for 41 years versus 43 years: 0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to 0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to 1.39; P0.01) as factors significantly associated with the probability of a live birth.Multiple repeat IVF cycles in women aged 41-44 years offers a reasonable long-term success rate. After six cycles of treatment, about 29% of women of advanced reproductive age using autologous oocytes expected to achieve a live birth. This information might assist in fertility counselling and managing patients' expectations by adjusting the appropriate treatment strategy and number of IVF cycle attempts, especially in countries in which egg donation is prohibited or when multiple repeated IVF cycles attempts are financially affordable.

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 Conclusions LH concentrations post-GnRHa trigger differ in regard to antagonist–agonist intervals, but the follicle/mature oocyte ratio achieved was not affected.

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.

Is physical activity after embryo transfer, as assessed by a smart band activity tracker, associated with decreased pregnancy rates?Prospective observational cohort study comprising infertile women aged38 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.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.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.

Objective To investigate whether the addition of embryo biopsy performed during preimplantation genetic testing for monogenic diseases is associated with a higher risk of obstetric and neonatal complications compared with in vitro fertilization (IVF) without preimplantation genetic testing or spontaneously conceived pregnancies. Methods This is a cohort study of all pregnancies conceived after preimplantation genetic testing for monogenic diseases (PGT-M group) from 2006 to 2018 at Sheba Medical Center, Israel. The control groups included patients who had conceived spontaneously (spontaneous conception group) or by IVF without preimplantation genetic testing (IVF group) and delivered at Sheba Medical Center. The obstetrics outcomes were compared among the groups. Multivariable regression modeling was performed, focusing on the relationship between preimplantation genetic testing and adverse outcomes. Results Final analysis included 345 singleton and 76 twin deliveries in the PGT-M group. The spontaneous conception group included 5,290 singleton and 92 twin deliveries. The IVF group included 422 singleton and 101 twin deliveries. Among singleton pregnancies, patients in the PGT-M group had a higher rate of hypertensive disorders (6.9%) compared with those in the spontaneous conception group (2.3%; odds ratio [OR] 3.3; 95% CI 1.9-4.8; adjusted odds ratio [aOR] 14.8; 95% CI 7.4-29.8) and the IVF group (4.7%; OR 1.5; 95% CI 0.8-2.7; aOR 5.9; 95% CI 1.9-18.2). Likewise, patients in the PGT-M group had a higher rate of small-for-gestational age neonates (12.4%) compared with those in the spontaneous conception group (3.9%; OR 3.4; 95% CI 2.4-4.9; aOR 2.3; 95% CI 1.5-3.4) and the IVF group (4.5%; OR 3; 95% CI 1.7-5.2; aOR 2.5; 95% CI 1.7-5.2). Among twin pregnancies, patients in the PGT-M group also had an increased rate of hypertensive disorders compared with those in the spontaneous conception group (4.3%; OR 4.1; 95% CI 1.2-13.3; aOR 10.9; 95% CI 2.3-50) and the IVF group (4%; OR 4.5; 95% CI 1.4-14.7; aOR 3.7; 95% CI 1.1-12.8). Conclusion Pregnancies conceived after preimplantation genetic testing for monogenic disorders were associated with an increased risk of obstetric complications compared with pregnancies conceived spontaneously or by IVF without preimplantation genetic testing.

OBJECTIVES: This study aimed to evaluate the role of intracytoplasmic sperm injection (ICSI) in the treatment of non-male factor infertile patients aged ≥ 39. METHODS: This is a single-center, prospective, randomized controlled clinical trial, between March 2018 and December 2019. Sixty-nine patients were recruited, and sixty patients participated in the study. Their ovaries were randomized prior to the beginning of the ovarian stimulation: the oocytes from one side (n = 257) were allocated to the ICSI (ICSI arm), while those of the contralateral side (n = 258) were allocated to conventional insemination (IVF arm). The fertilization rate per oocyte retrieved, number of zygotes (2PN), and cleavage-stage embryos were assessed and compared between the two study groups. RESULTS: The average number of zygotes (3.1 vs. 2.7 p = 0.45), the fertilization rate (72.4% vs. 65.1% p = 0.38), the average number of cleavage-stage (2.8 vs. 2.4 p = 0.29), and the average top-quality embryos (TQE) cleavage-stage embryos (1.7 vs. 1.6 p = 0.94) were comparable between the two groups. The TQE rate per randomized oocyte (41.2% vs. 41% p = 0.8) was also similar in both groups. CONCLUSIONS: ICSI does not improve the reproductive outcomes of advanced-age patients undergoing conventional insemination for non-male factor infertility. TRIAL REGISTRATION: NCT03370068

To assess the variables that may predict which cleavage-stage embryo may develop into a blastocyst, and vice versa, to determine whether the cleavage-stage embryo morphology should be taken into consideration when transferring the embryo at the blastocyst stage. A single center, retrospective cohort study. The study cohort included 3072 patients undergoing 3607 retrieval cycles and 23,124 embryos at the cleavage stage. We assessed the blastulation rate and evaluated which variables impact the ongoing pregnancy rate. High blastulation rate correlates with higher embryos' grading (I > II > III > IV > V) and higher number of blastomeres (8 > 7 > 6 > 5 > 4). 949 patients had fresh single blastocyst transfers. The ongoing pregnancy rate was 28.9% per transfer. Patients with ongoing pregnancies were significantly younger (34.3 vs. 36 years, p

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.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 pHlt;7.1, 5 min Apgar score ≤7, and/or neonatal intensive care unit admission.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 lt; 0.001) compared with primary MSAF.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.

While most studies focused on the association between the number of oocytes retrieved and LBR, there is lack of analysis highlighting the effect of the number of oocyte retrieved on top quality embryo (TQE) rate in different age groups. We aimed to study the correlations between the number and ratio of TQE, as assessed by morphology only, according to the number of oocytes retrieved, and to evaluate the impact of patients' age. This was a retrospective study that includes 1639 patients who underwent 2263 IVF cycles between 2016 and 2019. Patients were categorized into four groups according to the number of oocytes retrieved: 1-3, 4-9, 10-14, or 15 oocytes (OPU groups A-D, respectively). Another classification was according to patient's age 35, 35-40, and 40 years. Morphologically, TQE (both cleavage stage and blastocyst) was defined as those eligible for transfer or vitrification. TQE was assessed both as a fraction of oocytes retrieved per patients (rate) and the average TQE per number oocytes retrieved category. For all age subgroups, a negative significant association was observed between the number of oocytes retrieved and TQE rate (56.1%, 43.6%, 35.9%, and 34.3% for groups A-D, respectively). The reduction was significant up to 14 oocytes retrieved and plateau thereafter. On the other hand, TQE rate was significantly increased as women age increased, from 36.1% TQE rate in young women ( 35 years) to 40.3% for 35-40 years to 42.5% in older patients ( 40 years). Finally, a linear regression revealed a drop in TQE rate of - 0.5% for every oocyte retrieved, while an increased in TQE rate of + 0.7%, as the women age increased by 1 year. While young women are able to recruit more oocyte, including medium/low quality, older women recruit less oocytes, with good quality, as demonstrated by their higher morphologically TQE rate relative to the number of oocyte retrieved.

To evaluate the effect of large follicular size (≥24 mm) at day of oocyte retrieval on oocyte/embryo quality.A cohort study was conducted in a single tertiary medical center between July 2018 and May 2019. Before ultrasound-guided follicular aspiration, follicles were measured and divided into 2 groups according to their maximal dimensional size: large: ≥24 mm and normal:24 mm. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization, and embryo quality.428 follicles were measured, including 383 (62.81%) in the normal and 45 (14.06%) in the large follicle groups. Oocytes were achieved during aspiration from 297 (75.5%) and 29 (64.4%) of the normal and large follicle groups, respectively (p = 0.05). No in-between group differences were observed in mature oocyte (MII), fertilization, and top-quality embryo (TQE) rates. Nevertheless, once a zygote (2PN) was achieved, a trend toward a higher TQE rate/2PN was found in the large follicle group (16/19 [84.2%] vs. 115/171 [67.3%]; p = 0.062).While a nonsignificant decrease in oocyte recovery rate was found in follicles ≥24 mm, the zygote and TQE per follicle were comparable.

Aim: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase. Patients and Methods: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle. Results: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%). Conclusions: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients’ subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients. Design: Cohort historical, proof of concept study. Setting: Tertiary, University affiliated Medical Center. Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only "genuine" poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU. Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables. Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation. Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating "genuine" poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

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 (

Aim: This study evaluated the competency of oocytes/embryos derived from follicles >15 mm in diameter from obese patients, compared with nonobese patients. Patients and Methods: A cohort study was conducted in a single tertiary medical center between July 2018 and May 2019. Before ultrasound-guided follicular aspiration, follicles were measured and those with maximal dimensional size >15 mm were tracked. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization, and embryo quality. Results: 457 follicles were measured: 380 (83.2%) in nonobese and 77 (16.8%) in obese patients. No in-between group differences were observed in the causes of infertility, patients’ demographics, or ovarian stimulation characteristics. Oocytes were achieved during aspiration from 277 (72.8%) and 54 (70.0%) of the nonobese and obese groups, respectively (p = 0.67). No in-between group differences were observed in fertilization (2PN/oocyte), top quality embryo (TQE) per zygote (2PN), and TQE per follicle. Conclusion: Oocyte recovery rate from follicles >15 mm is unrelated to patients’ BMI. Moreover, the oocytes recovered from obese patients are competent yielding comparable zygote and TQE per follicle/oocyte, compared with nonobese patients. Further investigation is required to strengthen this finding.

OBJECTIVES To determine the rate of pregnancy complications and adverse obstetric and neonatal outcomes of twin pregnancies that were reduced to singleton at an early compared with a later gestational age. METHODS This was a historical cohort study of dichorionic diamniotic twin pregnancies that underwent fetal reduction to singletons in a single tertiary referral center between January 2005 and February 2017. The study population was divided into two groups according to gestational age at fetal reduction: those performed at 11-14 weeks' gestation, mainly at the patient's request or as a result of a complicated medical or obstetric history; and selective reductions performed at 15-23 weeks for structural or genetic anomalies. The main outcome measures compared between pregnancies that underwent early reduction and those that underwent late reduction included rates of pregnancy complications, pregnancy loss, preterm delivery and adverse neonatal outcome. RESULTS In total, 248 dichorionic diamniotic twin pregnancies were included, of which 172 underwent early reduction and 76 underwent late reduction. Although gestational age at delivery was not significantly different between the late- and early-reduction groups (38 weeks, (interquartile range (IQR), 36-40 weeks) vs 39 weeks (IQR, 38-40 weeks); P = 0.2), the rates of preterm delivery

With the recent increased utilization of oocyte vitrification for the purpose of fertility preservation, information regarding the future fertility potential of the frozen oocytes is mandatory. Nowadays, there is a relative lack of data about prediction of assisted reproductive technique (ART) success relying on the retrieved oocytes. In the present study, we therefore aimed to investigate whether oocyte diameter might predict the quality of the developing embryo. A retrospective, single-center cohort study. Oocytes retrieved following controlled ovarian hyperstimulation cycles during 2016 and incubated in a time-lapse incubator system were analyzed. Oocytes were grouped by mean oocyte diameter (MOD) and incubated for 5 days before the final morphological evaluation done by an expert embryologist. A total of 471 cycles which yielded 3355 metaphase II oocytes were included in the analysis. Embryos developed from oocytes with MOD close to the average (Average 1SDMODAverage + 1SD) had increased good-quality blastulation rates compared with embryos that developed from very small or very large oocytes. Oocytes with MOD between 105.96 and 118.69 μm have better probability of becoming top-quality D5 blastocysts (17.1-17.4% grade 1 embryos). There is a correlation between oocyte's MOD and the embryo quality at day 5. The oocytes with near average MOD have a better chance to develop to a good-quality embryo. Therefore, the study suggests that MOD might serve as a predictor for embryo grading at day 5.

Background Fragile X premutation (Amplification of CGG number 55–200) is associated with increased risk for fragile X-Associated Premature Ovarian Insufficiency (FXPOI) in females and fragile X-associated tremor/ataxia syndrome (FXTAS) predominantly in males. Recently, it has been shown that CGG repeats trigger repeat associated non-AUG initiated translation (RAN) of a cryptic polyglycine-containing protein, FMRpolyG. This protein accumulates in ubiquitin-positive inclusions in neuronal brain cells of FXTAS patients and may lead to protein-mediated neurodegeneration. FMRpolyG inclusions were also found in ovary stromal cells of a FXPOI patient. The role of FMRpolyG expression has not been thoroughly examined in folliculogenesis related cells. The main goal of this study is to evaluate whether FMRpolyG accumulates in mural granulosa cells of FMR1 premutation carriers. Following FMRpolyG detection, we aim to examine premutation transfected COV434 as a suitable model used to identify RAN translation functions in FXPOI pathogenesis. Results FMRpolyG and ubiquitin immunostained mural granulosa cells from six FMR1 premutation carriers demonstrated FMRpolyG aggregates. However, co-localization of FMRpolyG and ubiquitin appeared to vary within the FMR1 premutation carriers’ group as three exhibited partial ubiquitin and FMRpolyG double staining and three premutation carriers demonstrated FMRpolyG single staining. None of the granulosa cells from the five control women expressed FMRpolyG. Additionally, human ovarian granulosa tumor, COV434, were transfected with two plasmids; both expressing 99CGG repeats but only one enables FMRpolyG expression. Like in granulosa cells from FMR1 premutation carriers, FMRpolyG aggregates were found only in COV434 transfected with expended CGG repeats and the ability to express FMRpolyG. Conclusions Corresponding with previous studies in FXTAS, we demonstrated accumulation of FMRpolyG in mural granulosa cells of FMR1 premutation carriers. We also suggest that following further investigation, the premutation transfected COV434 might be an appropriate model for RAN translation studies. Detecting FMRpolyG accumulation in folliculogenesis related cells supports previous observations and imply a possible common protein-mediated toxic mechanism for both FXPOI and FXTAS.

To study the association between follicle size and oocyte/embryo quality, as a function of different triggering modes for final follicular maturation.Cohort study conducted in a single tertiary medical centre between July 2018 and May 2019. All women undergoing ovarian stimulation with triggering using human chorionic gonadotrophin (HCG), gonadotrophin-releasing hormone (GnRH) agonist or dual trigger (GnRHa + HCG) were included. Before ultrasound-guided follicular aspiration, follicles were measured and divided into three groups according to maximum dimensions: large ≥16 mm, medium 13-15 mm and small13 mm. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization and embryo quality.A total of 640 follicles were measured, including 402 (62.8%) in the large, 148 (23.1%) in the medium and 90 (14.1%) in the small groups. Oocytes were obtained during aspiration from 76.3%, 70.3% and 55.6% of the large, medium and small follicle groups, respectively (P = 0.001). The mature oocyte (metaphase II) rate was significantly higher in the large (P = 0.001) and medium (P = 0.01) compared with the small follicle group. Nevertheless, no between-group differences were observed in fertilization or top quality embryo rates among mature oocytes regardless of the size of the follicle from which they originated. Triggering mode did not influence oocyte recovery rate in the different follicle size groups.A higher oocyte recovery rate was observed from follicles13 mm, however, mature oocytes achieved similar fertilization and top quality embryo rates regardless of follicle size. Triggering mode did not influence oocyte recovery rate.

STUDY QUESTION Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone? SUMMARY ANSWER Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone. WHAT IS KNOWN ALREADY hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates STUDY DESIGN, SIZE, DURATION A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT). PARTICIPANTS/MATERIALS, SETTINGS, METHODS One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment. MAIN RESULTS AND THE ROLE OF CHANCE One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m2 versus 23.7 kg/m2) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43–1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR= 1.98 (1.05–3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group. LIMITATIONS, REASONS FOR CAUTION None. WIDER IMPLICATIONS OF THE FINDINGS The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by TRIO Fertility. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER ClinicalTrials.gov identifier: NCT02703584 DATE OF TRIAL REGISTRATION March 2016 DATE OF FIRST PATIENT'S ENROLLMENT May 2016

PURPOSE: Recent studies have focused on transvaginal ultrasound measurement (TVUS) of sub-endometrial contractility and computer-enhanced 3-D modeling scoring of the endometrium prior to embryo transfer (ET).The aim of this study was to compare pregnancy outcome of patients who performed the 3-D scoring or the sub-endometrial measurement prior to the ET with patients that did not perform those procedures. METHODS: A single center retrospective cohort study of 635 freeze/thaw cycles of blastocysts vitrified on day 5 and transferred between January 2016 and August 2016. RESULTS: We compared the patients who performed 3-D scoring with the control group and found comparable patients’ characteristics, clinical pregnancy rates (42% vs. 44.3, p = NS, respectively), and ongoing pregnancy rates (31.7% vs. 33.9%, p = NS).We then compared the patients who performed the sub-endometrial wave measurements with the control group and found similar findings. The clinical pregnancy rate (38.2% vs. 44.3, p = NS, respectively) and the ongoing pregnancy rate (30.8% vs. 33.9%) were comparable between the two groups. We performed a regression analysis to examine the independent contribution of different variables to the ongoing pregnancy rates. Both the 3-D and the wave count procedures were not found to have any influence on the ongoing pregnancy rates. CONCLUSIONS: Although new ultrasonic methods of evaluating the endometrium have been proposed during the last years, these methods have not been shown to improve the pregnancy rates compared to the original method of assessing the endometrium by measuring the endometrial thickness.

Background Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only. Methods A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits. Results The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p

Our aim was to assess the preimplantation embryos' sex ratios in couples with four or more children of same sex, undergoing sex selection for nonmedical reasons. We conducted a cohort-historical study of all consecutive patients admitted to the IVF-PGD program in a large tertiary center. We reviewed the computerized files of all consecutive women admitted to our IVF for sex selection for nonmedical reasons. Patients and their PGD cycle characteristics were compared according to the desired sex of their embryo and the mode of fertilization. Nine patients underwent a total of 19 PGD cycle attempts during the study period. Of the 77 embryos with complete molecular diagnosis, 41 revealed a male embryo and 36 a female embryo. Thirty-five percent of all the diagnosed embryos were of the desired sex. For couples desiring a boy, IVF cycles achieved a higher ratio of the desired embryonal sex compared to ICSI (52% vs 18.7%, p = .03). For couples desiring a girl, ICSI cycles had a higher percentage of the desired embryonal sex compared to IVF cycles (38% vs 23%). Moreover, 29.7% of ICSI and 40% of IVF embryos achieved the desired sex. In conclusion, PGD for sex selection results in a relatively low percentage (35%) of embryos demonstrating the desired sex. Nonetheless, selecting the mode of fertilization (ICSI/IVF) might improve the success rate. Further studies are required to explore the appropriate and cost-effective method for sex selection for nonmedical reasons.

The current systematic review and meta-analysis evaluate the perinatal outcomes in twin pregnancies following multifetal pregnancy reduction (MPR) compared with non-reduced triplet pregnancies. All studies comparing perinatal outcome of twin pregnancies following MPR to non-reduced triplet pregnancies were considered. MEDLINE, non-indexed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science were searched for relevant published articles up to August 2016. The search yielded 653 publications of which 92 were assessed for eligibility. A total of 24 studies met the inclusion criteria. Overall, the outcomes of pregnancies following MPR were better compared with expectantly managed triplets. The MPR group delivered at a later gestational age and was less likely to be delivered before 32 or 28 weeks' gestation. Newborns in the MPR group had significantly higher birthweight at delivery (mean difference 500 g [95% CI 439.95, 560.04]). Rates of pregnancy loss before 24 weeks' gestation and overall infant survival were comparable between the groups. This meta-analysis suggests that MPR of triplet pregnancies to twins is associated with improved perinatal outcome compared with non-reduced triplets. Should primary prevention of high order multiple pregnancy fail, MPR is an appropriate alternative to minimize the perinatal morbidity and mortality of triplet pregnancies.

Background For the last year we have been treating normal responders with gonadotropins and letrozole during the whole stimulation in order to improve response to FSH by increasing the intrafollicular androgen concentration, and to reduce circulating estrogen concentrations. The aim of this study was to compare the IVF outcome of normal responders treated with letrozole and gonadotropins during ovarian stimulation with patients treated with gonadotropins only. Methods A single centre retrospective cohort study of 174 patients (87 in each group). Results The age of the patients was comparable between the groups. Estradiol levels were significantly higher in the control group (6760 pmol/L vs. 2420 pmol/L respectively, p

Multifetal pregnancy reduction (MPR) is an accepted method of reducing complications of triplet pregnancies and higher-order multifetal pregnancies. Eighty-three pregnancies that underwent early (68 weeks) transvaginal MPR were compared with 125 pregnancies that underwent late (11-14 weeks) transabdominal MPR. Rates of pregnancy loss, preterm delivery, gestational diabetes and hypertensive disorders were similar among both groups. Early MPR was associated with a lower risk for small for gestational age newborns (6.5% versus 19.2%; P = 0.034; OR 0.32; 95% CI 0.11 to 0.92) and a higher risk for single-fetus loss (6% versus 0.8%; P = 0.041; OR 10.58; 95% CI 1.1 to 101.94). Preterm delivery rates seemed to be similar between the two groups. In MPR from triplets, an apparent benefit was observed for early MPR in preterm deliveries before 37 weeks, whereas, in MPR from high-order pregnancies, a benefit was observed for late MPR in deliveries before 32 weeks. Perinatal outcomes of twin pregnancies after early and late MPR seem to be grossly similar. Optimal timing for multifetal reduction depends on other factors, namely, the selectivity of the procedure and patient's preference.

Does fetal reduction of triplet pregnancies to singleton result in superior obstetric and neonatal outcomes compared with triplets reduced to twins?A historical cohort study including 285 trichorionic and dichorionic triplet pregnancies that underwent abdominal fetal reduction at 11-14 weeks in a single tertiary referral centre. The study population comprised two groups: reduction to twins (n = 223) and singletons (n = 62). Main outcome measures were rates of pregnancy complications, preterm delivery and neonatal outcomes. Non-parametric statistical methods were employed.Triplet pregnancies reduced to twins delivered earlier (36 versus 39 weeks, P0.001) with higher prevalence of Caesarean section (71.1% versus 32.2%, P0.001) compared with triplets reduced to singletons. Preterm delivery rates were significantly higher in twins compared with singletons prior to 37 weeks (56.9% versus 13.6%, P0.001), 34 weeks (20.2% versus 3.4%, P = 0.002) and 32 weeks (9.6% versus 0%, P = 0.01). No significant difference was found in the rate of pregnancy loss before 24 weeks (1.3% in twins versus 4.8% in singletons, P = 0.12) or in the rate of intrauterine fetal death after 24 weeks (0.4% versus 0%, P = 1.0). Both groups had comparable obstetrical complications and neonatal outcomes, except for higher rates of neonatal intensive care unit admission in twins (31.9% versus 6.8%, P0.001).Reduction of triplets to singletons rather than twins resulted in superior obstetric outcomes without increasing the procedure-related complications. However, because the rate of extreme prematurity in pregnancies reduced to twins was low, the overall outcome of those pregnancies was favourable. Therefore, the option of reduction to singletons should be considered in cases where the risk of prematurity seems exceptionally high.

We aim to retrospectively evaluate the role of increasing the gonadotropin daily dose from 450 IU/day to 300 IU twice a day on IVF-ET outcome in poor responder patients. All consecutive women admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU, followed by an IVF cycle using 300 IU twice a day, were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate was assessed. Twenty-three patients undergoing both cycles were evaluated. While there was no between-group difference in the duration of COH, number of 2PN embryos, fertilization rate and number of embryos transferred, patients receiving daily gonadotropin 300 IU twice a day achieved a significantly higher peak estradiol levels (3350.39 ± 2364.26 vs. 2223.74 ± 1299.91

Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on

Purpose We aim to estimate the future fertility of patient undergoing their first IVF cycle attempt with no oocyte retrieved, and to identify factors that might predict those who will conceive in subsequent IVF cycle attempt. Methods A cohort retrospective study of all consecutive women attending our IVF unit, for their first IVF cycle attempt, between January 2013 to December 2019, who reached the ovum pick-up (OPU) stage with zero oocyte retrieved. Patients’ characteristics and infertility-treatment-related variables in the first IVF cycle attempt were compared between those who conceived in a subsequent cycle and those who did not. Moreover, infertility-treatment-related variables during successful cycles resulting in pregnancy were compared to those without. Results 59 met the study inclusion criteria, yielding zero oocytes. During the follow-up period, 12 (20.3%) women conceived (one conceived twice), and 8 (14%) gave birth to a live infant. Cumulative live-birth rate per OPU and per patients were 4% and 14%, respectively. Clinical pregnancies were achieved after 3.61+1.4 cycle attempts (range: 1–6), with no live-births following the fifth IVF cycle attempt. No in-between group differences were observed in ovarian stimulation variables of their first IVF cycle attempt. Moreover, in those cycles resulting in pregnancy, patients achieved a significantly higher number of fertilized oocytes (2.15+1.5 vs 0.94+1.5, respectively; p Conclusion Women yielding zero oocytes at their first IVF cycle attempt, may achieve 14% cumulative live-birth rate after 5 IVF cycle attempts. Moreover, those who conceived in subsequent IVF cycle attempts were those achieving 2 or more fertilized oocytes/TQE.

The aim of this study was to compare the pregnancy rates between good quality blastocysts vitrified on day 6 versus blastocysts vitrified on day 5 after fertilization. This is a retrospective cohort study of 791 freeze-thaw cycles of blastocysts vitrified either on day 5 or on day 6 and transferred between January 2012 and October 2015. Five hundred and thirty-seven cycles included blastocysts vitrified on day 5, and 254 cycles included blastocysts vitrified on day 6. The age of the patients and the proportion of embryos that survived the thawing process were comparable between the two groups. More good quality embryos were transferred in the group in which blastocysts were vitrified on day 6 (1.2 vs. 1.3, p = 0.005), but the clinical pregnancy rate (44 vs. 33 %, p = 0.002) and the ongoing pregnancy rate (41 vs. 28 %, p

Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. In the present study, we aim to evaluate the outcome of natural cycle FET with modified luteal support. All consecutive patients undergoing natural or artificial hormone replacement (AHR) day-2/3 FET cycles between May 2012 and June 2015 in our IVF unit were evaluated. While AHR FET cycles were consistent, those undergoing natural cycle FET received progesterone luteal support, and from June 2014, patients received two additional injections, one of recombinant hCG and the other of GnRH-agonist, on day of transfer and 4 days later, respectively (modified luteal support). Patients’ clinical characteristics and laboratory/embryological variables were comparable between those undergoing natural vs. AHR cycles, during the earlier as compared to the later period. Moreover, while implantation, clinical, and ongoing pregnancy rates were significantly higher during the later period in patients undergoing the natural cycle FET with the modified luteal support (31, 51, and 46 %, respectively), as compared to natural (17, 26, and 20 %, respectively), or AHR FET in the late study period (15, 22, and 17 %, respectively), the natural cycle FET without the additional two injections yielded the same results, as the AHR cycles. We therefore suggest that in ovulatory patients undergoing FET, natural cycle FET with the modified luteal support should be the preparation protocol of choice. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

PURPOSE: A few years ago, we started to use a new freeze–thaw protocol for the frozen embryo transfer cycles. Instead of thawing the embryos 2–4 h prior to the transfer, we started thawing the embryos 20–22 h prior to the transfer. The aim of this study was to compare the pregnancy rate in cases of embryos that continued to develop in the post-thawing culture to that of embryos that did not. METHODS: A retrospective cohort study of blastocyst freeze/thaw cycles vitrified on day 5, thawed and transferred after 20–22 h in the culture, between January 2012 and December 2016. RESULTS: A total of 375 patients were included in the analysis. Two hundred twenty-eight embryos graded as good, 87 graded as fair, and 60 graded as poor embryos were transferred. The clinical pregnancy rate (50% vs. 19.5% vs 3.3% p