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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.

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

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

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.

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

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

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

Objective To describe and compare the ongoing pregnancy rate between morulae and cavitating morulae (CAVM) transferred on day 5, to describe and compare the blastulation rate between day 5 morulae and CAVM, and to describe the pregnancy rate of these slow-developing blastocysts during a frozen embryo transfer (FET) cycle. Design Retrospective cohort study. Setting Single tertiary care medical center. Patient(s) Delayed-development embryos: 3,321 cycles that included 10,304 embryos on day 5 that were cultured until day 6. Intervention(s) Development of morula and CAVM to the blastocyst stage. Main Outcome Measure(s) Blastulation rate. Result(s) The fresh embryo transfers comprised 186 patients with 82 embryos at the morula stage and 104 embryos at the CAVM stage. The pregnancy rate (15.8% vs. 21.1%) and the ongoing pregnancy rate (15.8% vs. 17.3%) were comparable between the groups. The study group included 10,304 day-5 delayed embryos: 5,395 morulae and 4,909 CAVM on day 5. The blastulation rate was statistically significantly higher in the CAVM group compared with the morula group (39.2% vs. 20.4%). We included 201 FET cycles: 77 warmed blastocysts that developed from a morula on day 5 and 124 warmed blastocysts that developed from CAVM on day 5. The clinical pregnancy rate was comparable between the two groups per embryo transfer (21.3% vs. 24.7%). Conclusion(s) Transferring of fresh, slow-developing embryos seems to improve the cycle outcomes compared with culturing for another day and then vitrifying and thawing later.

PURPOSE: The aim of the present study was to determine the percentage of infertility patients who are diagnosed with a non-receptive endometrium according to the endometrial receptivity array (ERA) test and to examine whether adjusting the embryo transfer day according to the proposed shift in the window of implantation improves the pregnancy rate compared to non-ERA-tested patients. METHODS: A single-center retrospective cohort study, including 53 consecutive good prognosis patients (0–2 previous frozen embryo transfers) admitted to our IVF unit for a mock cycle prior to their frozen day-5 embryo (blastocyst) transfer cycle. The mock cycle included an endometrial biopsy for both the ERA test and histological assessment by the Noyes criteria (study group). The next cycle frozen embryo transfer (FET) in the study group was adjusted according to the ERA results. The control group consisted of patients who underwent FET cycles at our clinic during the same period, without performing the endometrial biopsy and ERA testing. RESULTS: During the study period, 503 patients (control group) underwent FET cycles without performing the ERA testing and 41 patients had FET following an ERA test. There were no between-group differences in patients’ age, number of previous transfers, endometrial thickness, number of transferred embryos, and ongoing pregnancy rates (35.2 vs. 39%, respectively, p = NS). Out of the 53 patients who performed the ERA test before their first or second FET, five endometrial samples (9.4%) were found to be post-receptive, 29 (54.7%) pre-receptive, and only 19 samples (35.8%) were receptive. Women in the study group with pre- or post-receptive endometrium on ERA testing, the appropriate adjustment in timing of FET according to the ERA test resulted in a 33.3% pregnancy rate, which is comparable to the 35.2% background ongoing pregnancy rate of the control group. CONCLUSIONS: Performing the ERA test in a mock cycle prior to a FET does not seem to improve the ongoing pregnancy rate in good prognosis patients. Further large prospective studies are needed to elucidate the role of ERA testing in both good prognosis patients and in patients with recurrent implantation failure.

Many Patients with persistent retained products of conception prefers to avoid surgical interventions, such as a dilatation and curettage (D&C) that might pose an additional future risk to their already compromised fertility or obstetric performance. The aim of this study was to the possibility of induced withdrawal bleeding following oral contraceptive administration as a non-surgical treatment for patients with persistent retained products of conception (RPOC). A retrospective study of patients presenting with retained products of conception (RPOC) after failed expectant management or after treatment with PGE1 was performed. Twelve women presenting with RPOC at ≤8 weeks gestation with minimal to mild vaginal bleeding and no signs of infection were treated with oral contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%) successfully expelled the RPOC after completing the three-week course of OCPs. The three cases (25%) that did not resolve following OCP treatment had pregnancy products with positive blood flow on Doppler examination. We conclude that OCPs may be a useful medical treatment option for persisting RPOC in selected patients with absence blood flow on Doppler examination wishing to avoid surgical intervention.

Objective To assess clinical outcome among infertile couples treated by in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) using testicular sperm from azoospermic cancer survivors. Study design This clinical retrospective study included infertile couples treated in a single tertiary referral center between 1996 and 2013. All male partners were cancer survivors who were diagnosed with azoospermia due to previous gonadotoxic treatments and referred to testicular sperm extraction (TESE). Retrieved sperm was used for IVF-ICSI among patients’ spouses. Sperm retrieval rate and IVF-ICSI outcome were evaluated. Results Sperm was successfully retrieved in 12 out of 36 patients (33.3%) on initial TESE, with an overall sperm retrieval rate of 38.6% (17 of 44). Female patients were 29.8 ± 5.1 years old. The average number of retrieved oocytes was 14.0 ± 4.0 per cycle, with clinical pregnancy and live birth rates per successful TESE of 64% (11 of 17) and 58.8% (10 of 17), respectively. Age, serum FSH, testicular volume and time from chemotherapy to TESE were not significantly different between patients with successful TESE to those without. Patients suffering from seminomas had significantly higher sperm retrieval rate, as compared to patients who had Hodgkin’s lymphoma (P = 0.024). Conclusions Post-chemotherapy azoospermia can be successfully treated with TESE and ICSI, and should be offered to azoospermic cancer survivors who did not cryopreserve sperm prior to their gonadotoxic treatments.

To examine whether patients with poor ovarian response (POR) during conventional IVF/intracytoplasmic sperm injection (ICSI) treatment cycle may benefit from a modified natural cycle (MNC)-IVF.Cohort historic study.Tertiary, university-affiliated medical center.One hundred eleven patients with POR, defined according to the Bologna criteria, who underwent a subsequent MNC-IVF within 3 months of the previous failed conventional IVF/ICSI cycle. The elimination of bias in this selection, for the purposes of this study, was achieved by including only a subgroup of "genuine" poor responder patients, those who yielded up to three oocytes after controlled ovarian hyperstimulation (COH) with a minimal gonadotropin daily dose of 300 IU.Modified natural cycle IVF protocol with GnRH antagonist (GnRH-a) supplementation. Gonadotropin-releasing hormone antagonist treatment was started when a follicle of 13 mm was present. Two to three ampules of hMG were coadministered daily during the GnRH-a treatment.Live birth rate, pregnancy rate (PR), number of oocytes retrieved, and number of embryos transferred.Live birth rate in "genuine" poor ovarian responders was1%. Furthermore, in the subgroup of patients with POR who underwent a previous conventional IVF/ICSI cycle with a yield of only one oocyte, no pregnancies were achieved during the MNC-IVF cycle.Modified natural cycle-IVF is of no benefit for genuine poor ovarian responders and the option of egg donation should be seriously considered for this population.

Objectives: Chemerin, a novel adipocytokine, has been implicated in major metabolic and inflammatory processes. Study aims were to determine whether circulating maternal chemerin concentration (1) differs between pregnant and non-pregnant women, (2) changes as a function of gestational age, and (3) correlates with maternal insulin resistance. In addition, we investigated which compartment, maternal, fetal or placental, is the source of chemerin in maternal circulation. Methods: The study included three groups: Non-pregnant (n=18), pregnant women in the first trimester (n=19) and pregnant women in the third trimester (n=33). Chemerin was measured in cord blood and in maternal serum samples taken before and after delivery. Chemerin mRNA expression was evaluated in fetal and human adult tissues. Results: Chemerin serum concentration was significantly higher in pregnant women in the third trimester than in non-pregnant and pregnant women in the first trimester. Chemerin concentration positively correlated with body mass index (BMI) and insulin resistance. Antenatal chemerin concentration was significantly lower than that during the postpartum period. Neonatal chemerin did not correlate with maternal one. Chemerin mRNA expression was abundant in fetal and adult liver and omental fat, but relatively low in placenta. Conclusions: Chemerin is increased during normal gestation and is associated with maternal BMI and insulin resistance. Maternal tissues, possibly liver and adipose tissue, contribute to the increased maternal chemerin concentration.

To determine whether reduction of twin gestation to singleton pregnancy is associated with improved perinatal outcome.A retrospective cohort study.Single tertiary care medical center.A cohort of 63 singleton pregnancies after reduction from dichorionic-diamniotic twins gestation and 62 dichorionic-diamniotic nonreduced twins.Fetal reduction between 11 and 14 weeks of gestation.Obstetric outcome.The rates of preterm delivery at34 weeks (1.6% in pregnancies after reduction vs. 11.7% in nonreduced twins) and at37 weeks of gestation (9.5% vs. 56.7%) were significantly lower in patients whose pregnancies were reduced to singletons. The rates of miscarriage of one twin (0% vs. 4.8%) and early pregnancy loss before 24 weeks of gestation as well as the rates of gestational diabetes (11.1% vs. 10%), hypertensive diseases of pregnancy (6.3% vs. 15%), and intrauterine growth restriction (0% vs. 3.3%) were similar in both groups.Fetal reduction of twins to singleton is associated with a lower risk of prematurity and superior perinatal outcome compared with nonreduced twins. Therefore, the option of fetal reduction should be considered in certain cases of twin pregnancies, where the risk for adverse outcome seems exceptionally high.

Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant.This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0-12.3) in the ART group and 9.3 years (interquartile range 8.0-10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number.Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80-1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22-31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67-6.32).A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

Early pregnancy loss is common among women treated with assisted reproduction treatment, but whether it is a prognostic factor for success in subsequent IVF cycles is not well established. The aim of this study was to determine whether a biochemical pregnancy (BP) or spontaneous abortion (SA) affects the pregnancy rates in the following cycle. A retrospective study of 2687 women undergoing 6678 cycles between January 1998 and March 2010 was performed. Ongoing pregnancy rate (PR) per cycle was compared between patients with a pregnancy loss versus a negative β-HCG in their previous cycles. Multivariate analysis of factors affecting ongoing pregnancy rate was performed. BP and/or SA in the first three cycles did not significantly alter the chances to conceive (16.9% patients with BP and/or SA in the previous cycle versus 16.5% patients with no previous pregnancy). From cycle 4 onwards, the presence of a previous abortion (either BP or SA) was associated with better ongoing PR (23.0% versus 11.2%, P

Objective To determine the efficacy of pre-emptive administration of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen vs. a placebo on pain relief during medical abortion and to evaluate whether NSAIDs interfere with the action of misoprostol. Design Prospective, double-blind, randomized, controlled study. Setting University-affiliated tertiary hospital. Patient(s) Sixty-one women who underwent first-trimester termination of pregnancy. Intervention(s) Patients received 600 mg mifepristone orally, followed by 400 μg oral misoprostol 2 days later. They were randomized to receive pre-emptively two tablets of 400 mg ibuprofen orally or a placebo, when taking the misoprostol. The patients completed a questionnaire about side effects and pain score and returned for an ultrasound follow-up examination 10–14 days after the medical abortion. Main Outcome Measure(s) Significant pain, assessed by the need for additional analgesia, and failure rates, defined by a need for surgical intervention. Result(s) Pre-emptive ibuprofen treatment was found to be more effective than a placebo in pain prevention, as determined by a significantly lower need for additional analgesia: 11 of 29 (38%) vs. 25 of 32 (78%), respectively. Treatment failure rate was not statistically different between the ibuprofen and placebo groups: 4 of 28 (14.2%) vs. 3 of 31 (9.7%), respectively. History of menstrual pain was predictive for the need of additional analgesia. Conclusion(s) Pre-emptive use of ibuprofen had a statistically significant beneficial effect on the need for pain relief during a mifepristone and misoprostol regimen for medical abortion. Ibuprofen did not adversely affect the outcome of medical abortion. Clinical Trial Registration Number NCT00997074.

OBJECTIVES The purpose of this study was to describe the characteristics and outcomes of umbilical cord hernias diagnosed prenatally. METHODS We conducted a retrospective study of all pregnancies with the diagnosis of a fetal umbilical cord hernia during a 5-year period. All women received care from a multidisciplinary team and underwent complete meticulous sonography for structural malformations as well as fetal echocardiography and amniocentesis. RESULTS Between 2004 and 2009, isolated fetal umbilical cord hernias were diagnosed in 8 pregnant women. The gestational ages at the time of referral ranged from 16 to 28 weeks (median, 20 weeks). In 1 case, intrauterine fetal death occurred at 35 weeks due to rupture of the umbilical cord. All remaining cases were delivered at 36 to 40 weeks, and the neonates underwent corrective surgery with good outcomes. CONCLUSIONS Despite 1 case complicated by intrauterine fetal death in this study, the outcome of an isolated fetal umbilical hernia seems favorable.

Objective To evaluate the influence of seasonal variation on in vitro fertilization (IVF) outcome in a large cohort population. Methods & materials A total of 5,765 IVF cycles conducted in Sheba medical center between 2013 and 2016 were retrospectively analyzed. The treatment cycles included 4214 ovarian stimulation and ovum pick up (OPU) cycles of which 3020 resulted in fresh embryo transfer and 1551 vitrified- warmed cycles of which1400 resulted in warmed embryo transfer. Cycles were assigned to seasons according to the date of OPU for fresh embryo transfer cycles or according to the date of embryo warming for vitrified warmed embryo transfer cycles. Results There were no statistically significant differences between the calendar months or seasons concerning the number of oocytes retrieved or fertilization rate in the fresh cycles. Throughout the 4 years of the study, the monthly clinical pregnancy rate fluctuated between 18.2% and 27.9% per fresh embryo transfer (mean 23.3%) and between 17.7% and 29.4% per vitrified warmed embryo transfer (mean 23%). These fluctuations did not follow any specific seasonal pattern. Conclusions Our study did not demonstrate any significant influence of the calendar months or seasons on the clinical pregnancy rates of fresh or vitrified warmed embryo transfers. It might be speculated that the complete pharmaceutical control of the ovarian and endometrial function, as well as the homogeneous treatments, procedures and laboratory equipment used during the study period have lowered the influence of seasonal effect on IVF treatment outcome.

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive β-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

Objective To assess the success rate of vaginal delivery among women with twin pregnancies; the Twin Birth Study has shown that vaginal delivery and caesarean section are equally safe for twin delivery but >40% of the planned vaginal delivery group delivered by caesarean section. Design A retrospective cohort study. Setting A tertiary medical centre. Population A total of 2194 women with twin pregnancies not complicated with very low birthweight. Methods Planned mode of delivery was documented in the woman's electronic record upon entering the delivery room. Information regarding maternal age at delivery, parity, gestational age, presentation, previous history of caesarean delivery, birthweight and Apgar score was collected from the obstetric electronic charts. Main outcome measured Rate of vaginal twin delivery. Results Of the 2194 women included, 1311 twin pregnancies had planned caesarean delivery and 883 underwent a trial of labour. Of the 883 women who underwent a trial of labour, the rate of vaginal delivery was 86.9%, whereas the rates of caesarean delivery and combined vaginal–caesarean delivery were 11.1% and 2.0%, respectively. Presentation of second twin, gestational age and maternal age did affect the chances of success. Nulliparity [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.4–4.05], Foley induction of labour (OR 2.33, 95% CI 1.38–3.91) and body mass index >30 kg/m2 (OR 1.76, 95% CI 1.03–3) were independent risk factors for caesarean delivery. Conclusions The rate of vaginal delivery among women with twin pregnancies who undergo labour can be high, especially in women who laboured spontaneously and have delivered before. Tweetable abstract The rate of vaginal delivery of twins can be high, especially in women who have delivered before.

We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome.All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose.Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate.In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.