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Objective: To study the perinatal outcomes of children born from different conception methods: in vitro fertilization (IVF) with autologous oocytes or IVF with donor egg vs. those conceived without medical assistance by using a sibling analysis., Design: Retrospective cohort study conducted using electronic medical record data from 2000 through 2018, of a national healthcare organization., Subjects: The cohort included mothers who had 2 pregnancies and their children. Cohort A compared women with 2 medically unassisted conceptions with those with an unassisted first conception followed by an IVF conception. Cohort B compared women with 2 medically unassisted conceptions with those with an unassisted conception followed by a second pregnancy from oocyte donation., Exposure: None., Main Outcome Measures: Perinatal outcomes, including small for gestational age (SGA) and preterm birth (PTB) at <37 weeks, were investigated. The secondary outcomes included low birth weight, very low birth weight, and large for gestational age (LGA)., Results: Cohort A comprised women who had 2 medically unassisted pregnancies and those with 1 medically unassisted pregnancy followed by IVF (n = 1,080 in each). Gestational age at delivery for the second conception was significantly lower in the unassisted + IVF group compared than in the medically unassisted group (38.1 ± 2.1 weeks vs. 39.1 ± 1.4 weeks). The unassisted + IVF group had higher rates of prematurity at <37 weeks (12% vs. 3.5%) and SGA than the medically unassisted group (5.4% vs. 3.4%). The adjusted odds ratio for PTB was 3.32 (95% confidence interval, 2.11-5.29), and that for SGA was 1.88 (95% confidence interval, 1.07-3.32). Cohort B included 94 women in each group. No differences were found between the medically unassisted and medically unassisted + donor egg groups regarding PTB at <37 weeks and SGA. The rate of LGA was higher in the egg donation group (24% vs. 16.5%)., Conclusions: This sibling analysis suggests that IVF pregnancies with autologous eggs are more susceptible to PTB, low birth weight, very low birth weight, and SGA, whereas donor egg pregnancies appear relatively unaffected, except for the higher rate of LGA., Competing Interests: Declaration of Interests H.S.R. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work. A.H.K. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work. E.H.-H. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work. M.L. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work. R.R.-K. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work. A.W. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work. N.M. reports funding from Maccabi Sick Fund Grant 2018 Research regarding family planning (egg donation in in vitro fertilization treatments) outside the submitted work., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Research Question: What are the safety and feasibility of repeated subcutaneous doses of gonadotrophin-releasing hormone (GnRH) agonist for luteal support in IVF cycles triggered by a GnRH agonist?, Design: In this prospective trial, patients exhibiting oestradiol concentrations of over 2500 pg/ml after use of a GnRH agonist for triggering ovulation were initially randomized to GnRH agonist luteal support (0.1 mg subcutaneously every other day, starting on day 3 after embryo transfer) or to a control group supported by 80 µg of recombinant human chorionic gonadotrophin (HCG) on day 3 after embryo transfer. All patients underwent a day 5 blastocyst transfer. Randomization to the HCG luteal support was stopped owing to two cases of ovarian hyperstimulation syndrome (OHSS) and the study was continued solely with GnRH agonist luteal support., Results: The study included 39 women in the repeated GnRH agonist luteal support group and seven in the HCG micro dose group. There were no cases of OHSS among patients supported by a GnRH agonist, and no other adverse events were recorded. There were no cases of bleeding before the pregnancy test, and hence no cases of an insufficient luteal phase. A clinical pregnancy rate of 43.6% was achieved with GnRH agonist luteal support. Hormone dynamics during the stimulation cycle reflected rising LH and progesterone concentrations after the introduction of GnRH agonist support., Conclusions: Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF?, Design: A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1-10 Visual Analogue Scale (VAS, referred to as the 'Stress Scale'. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed., Results: Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 μg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 μg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 μg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004)., Conclusion: It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Diastolic dysfunction may influence perioperative outcome, early graft function, and long-term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5-32.6] vs 22.4 [IQR 19.9-25.3] kg/m 2 ) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5-32.5] vs 17 [IQR 3-23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One-year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3-22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3-22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: To evaluate the safety of oocyte activation by calcium ionophore in cases of failed fertilization after intracytoplasmic sperm injection (ICSI) procedure with respect to birth defects., Design: A retrospective cohort of pregnancies achieved by oocyte activation with calcium ionophore after ICSI (ICSI-Ca) and routine ICSI between the years 2006 and 2014., Setting: Not applicable., Patient(s): The cohort included a total of 793 pregnancies: 66 (8%) were lost to follow up and 49 (6%) were ongoing pregnancies at the time of data collection. Out of the 678 available cases for analysis, 595 treatments were ICSI alone (88%) and 83 were ICSI-Ca (12%)., Intervention(s): None., Main Outcome Measure(s): Pregnancy and neonatal outcomes including birth defects were compared., Result(s): On the basis of a cohort of 595 ICSI pregnancies and 83 ICSI-Ca pregnancies, we found no difference in birth defects rate for singletons or for twins. Additionally, no significant difference was found between defect type (chromosomal aberration or structural malformations) and malformation type (heart, urogenital, and limb), between the ICSI and ICSI-Ca groups. Moreover, no significant differences were found regarding birth weight, gestational week at time of delivery, and fetal gender for singleton or twin pregnancies., Conclusion(s): Ca ionophore oocyte activation should be considered as a legitimate option for cases of failed or low fertilization by ICSI., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The aim of this comparative randomized embryology trial was to determine if an intravaginal culture device (IVC) can provide acceptable embryo development compared with conventional IVF. Ten women between the ages of 27 and 37 years with an indication for IVF treatment were included in this study. After ovarian stimulation, oocytes were randomized to fertilization in the IVC device or using conventional IVF. Fertilization rates were higher in the IVF group compared with the IVC device (68.7% ± 36 % versus 40.7% ± 27%), respectively, whereas cleavage rates were similar (93% ± 1.5% versus 97% ± 6%) for both groups. A significantly lower number of embryos of suitable quality for transfer was obtained from the IVC device compared with conventional IVF (OR, 0.47; 95% CI, 0.26 to 0.87). The clinical pregnancy rate from transfer of IVC device embryos was 30%. Satisfaction questionnaires were also completed by all participants. Most women (70%) placed high importance on having had fertilization and embryo development occur while carrying the device. Overall, the IVC device produced reasonable pregnancy rates suggesting this technology may have a place under certain circumstances. Cost-benefit analysis, psychological factors and future studies must be considered., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: Approximately 15% of the infertile population faces an ovulatory disorder; most of them classified as WHO class two anovulation [polycystic ovarian syndrome (PCOS) prototype]. Worldwide, this translates into millions of patients and emphasizes the need of a simple, effective and well tolerated method of ovulation induction. In this review, we will revisit letrozole use in the subset of WHO class two ovulatory problems and evaluate the contribution of the last year's literature to its practice., Recent Findings: In a multicentre, randomized controlled trial comparing letrozole with clomiphene in 750 PCOS patients having regular intercourse, live birth rates were significantly higher for the letrozole group [rate ratio 1.44, 95% confidence interval (95% CI) 1.10-1.87]. In a meta-analysis summarizing clinical trials testing aromatase inhibitors used alone or with other medical therapies for ovulation induction in PCOS patients, live birth rates were again significantly higher when letrozole was compared with clomiphene citrate [odds ratio (OR) 1.64, 95% CI 1.32-2.04]. A retrospective analysis of children born to infertile women assessed the congenital malformation rate after exposure to letrozole in comparison to clomiphene citrate and to natural conceptions. No significant differences in malformation rates were detected between the groups (2.9, 2.5 and 3.9%, respectively)., Summary: High-level evidence supports letrozole as the first drug of choice for ovulation induction in the PCOS population. The increasing use of letrozole with pregnancy follow-up provides additional reassurance for foetal safety.

Objective: To study the advantage of intracytoplasmic morphologically selected sperm injection (IMSI) versus intracytoplasmic sperm injection (ICSI) in the first artificial reproductive technology (ART) cycle and in consecutive cycles., Design: A cohort study., Setting: Single outpatient fertility center., Patient(s): Couples presenting with male factor infertility, requiring ovum micromanipulation., Intervention(s): The ICSI or IMSI was performed according to the couple's choice., Main Outcome Measure(s): Clinical intrauterine pregnancies and deliveries., Result(s): A total of 1,891 IVF-ICSI cycles and 577 IVF-IMSI cycles were included. In the first IVF treatment, pregnancy rates (PRs) were 46% and 47%, respectively, and delivery rates were 23% versus 30%, respectively. In the second cycle to follow a failed ICSI, PRs and delivery rates were significantly higher for patients who chose to shift to the IMSI technique compared with patients who chose to go through a second IVF-ICSI cycle (56% vs. 38% PRs and 28% vs. 18% delivery rates, respectively). In the following cycles a significant difference was demonstrated in both PR and delivery rates in favor of patients shifting between treatments. In a multivariate analysis an approximate threefold increased chance existed for both pregnancy and delivery only in the case of couples failing an ICSI attempt who shifted to IMSI., Conclusion(s): Our present experience supports refraining from repeated IMSI cycles. In light of improved PRs and delivery rates, we recommend promoting the IMSI method for couples who failed ICSI cycle, once or more., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)