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STUDY QUESTION Does the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have an association with ovarian reserve as expressed by circulating anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER Ovarian reserve as assessed by serum AMH levels is not altered at 3 months following mRNA SARS-CoV-2 vaccination. WHAT IS KNOWN ALREADY A possible impact of SARS-CoV-2 infection or vaccination through an interaction between the oocyte and the somatic cells could not be ruled out, however, data are limited. STUDY DESIGN, SIZE, DURATION This is a prospective study conducted at a university affiliated tertiary medical center between February and March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Study population included reproductive aged women (18–42 years) that were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart). Women with ovarian failure, under fertility treatments, during pregnancy, previous Covid-19 infection or vaccinated were excluded from the study. Blood samples were collected for AMH levels before the first mRNA vaccine administration. Additional blood samples after 3 months were collected for AMH and anti-Covid-19 antibody levels. Primary outcome was defined as the absolute and percentage change in AMH levels. MAIN RESULTS AND THE ROLE OF CHANCE The study group consisted of 129 women who received two mRNA vaccinations. Mean AMH levels were 5.3 (±SD 4.29) µg/l and 5.3 (±SD 4.50) µg/l at baseline and after 3 months, respectively (P = 0.11). To account for possible age-specific changes of AMH, sub-analyses were performed for three age groups: 35 years. AMH levels were significantly lower for women older than 35 years at all times (P = 0.001 for pre and post vaccination AMH levels versus younger women). However, no significant differences for the changes in AMH levels before and after vaccinations (Delta AMH) were observed for the three age groups (P = 0.46). Additionally, after controlling for age, no association was found between the degree of immunity response and AMH levels. LIMITATIONS, REASONS FOR CAUTION Although it was prospectively designed, for ethical reasons we could not assign a priori a randomized unvaccinated control group. This study examined plasma AMH levels at 3 months after the first vaccination. It could be argued that possible deleterious ovarian and AMH changes caused by the SARS-CoV-2 mRNA vaccinations might take effect only at a later time. Only longer-term studies will be able to examine this issue. WIDER IMPLICATIONS OF THE FINDINGS The results of the study provide reassurance for women hesitant to complete vaccination against Covid 19 due to concerns regarding its effect on future fertility. This information could be of significant value to physicians and patients alike. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by Sheba Medical Center institutional sources. All authors have nothing to disclose. TRIAL REGISTRATION NUMBER The study protocol was approved by the ‘Sheba Medical Center’ Ethical Committee Review Board (ID 8121-21-SMC) on 8 February 2021 and was registered at the National Institutes of Health (NCT04748172).

Objective To compare the effectiveness and safety of the oxytocin antagonist atosiban with conventional beta-adrenergic agonist (beta-agonist) therapy in the treatment of preterm labour. Design Three multinational, multicentre, double-blind, randomised, controlled trials. Setting Hospitals in Australia, Canada, Czech Republic, Denmark, France, Israel, Sweden, and the UK. Population Women diagnosed with preterm labour at 23-33 completed weeks of gestation. Methods Seven hundred and forty-two women were randomised; 733 received atosiban (n = 363; intravenous (iv) bolus dose of 6.75 mg, then 300 mug/minute iv. for 3h and 100 mug/min iv thereafter) or beta-agonist (n 379; ritodrine, salbutamol or terbutaline iv; dose titrated) for at least 18h and rip to 48 hours. Uterine contraction rate, cervical dilatation and effacement were used to assess progression of labour. An all patients treated analysis, using the Cochran-Mantel-Haenszel test, was performed. Main outcome measures Tocolytic effectiveness was assessed in terms of the number of women undelivered after 48 hours and seven days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Results There were no significant differences between atosiban and beta -agonists in delaying delivery for 48h (88.1% vs 88.9%; P = 0.99) or seven days (79.7% versus 77.6%; P = 0.28). Tocolytic effectiveness was also similar in terms of mean [SD] gestational age at delivery (35.8 [3.9] weeks vs 35.5 [4.1] weeks) and mean [SD] birthweight (2491 [813] g versus 2461 [831] g). Maternal side effects, particularly cardiovascular adverse events (8.3% vs 81.2%, P < 0.001) were reported more frequently in women given beta -agonists, resulting in more treatment discontinuations due to side effects (1.1% vs 15.4%, P = 0.0001). No statistical differences in neonatal/infant outcomes were observed with either study medication. Conclusions In the largest study of tocolytic therapy to date, atosiban was comparable in clinical effectiveness to conventional beta-agonist therapy, but was associated with fewer maternal cardiovascular side effects. We conclude that atosiban has clinical advantages over current tocolytic therapy.

PROBLEM: It is unclear how paternal leukocyte immunization prevents pregnancy loss. We investigated whether immunization affects early pregnancy, and whether it increases the rate of implantation and early embryonic development at the time of implantation. METHOD: Three groups of women with possible implantation failure were immunized: (1) recurrent biochemical pregnancies (>3), (2) three or more failed in vitro fertilization (IVF) cycles, and (3) IVF after immunization for recurrent abortion (>3). Patients were immunized if antipaternal complement-dependent antibody (APCA) was negative, and mixed lymphocyte culture hyporeactive to husbands lymphocytes. Immunizations were prepared from 100 ml paternal blood separated by Ficoll Hypaque density centrifugation. IVF was attempted after APCA was produced. RESULTS: In the women with biochemical pregnancies, 10 to 12 subsequent pregnancies developed normally. Seventy-nine subsequent IVF cycles in 33 patients resulted in 20 pregnancies, 16 of which developed normally. Six pregnancies followed 30 cycles in recurrent failed IVF, and 14 pregnancies from 49 cycles in 23 patients with previous habitual abortion. CONCLUSIONS: This treatment may prevent further biochemical pregnancies if control studies confirm this preliminary observation, but was not shown to affect recurrent failed embryo transfer.

To determine whether complete failure of fertilization of oocytes in couples with unexplained infertility persists during subsequent in vitro fertilization (IVF) cycles.A retrospective study of 120 cycles of IVF in 44 couples with unexplained infertility and complete failure of fertilization during their first IVF trial.In vitro fertilization unit of the Sheba Medical Center.Forty-four couples undergoing IVF for unexplained infertility.Fertilization rate of retrieved oocytes and pregnancy rate.Of the initial 44 couples, 37 underwent additional IVF cycles and 30 (81.1%) achieved fertilization. Seven patients conceived during the study period as a result of IVF and two conceived spontaneously.Complete failure of fertilization does not necessarily persist during subsequent IVF cycles. Therefore, at least two more IVF cycles should be attempted before reverting to other therapeutic options. However, although fertilization can be achieved in most couples, the mean oocyte fertilization rate during subsequent cycles in this group is low. This suggests an underlying undiagnosed pathology of oocyte/sperm interaction in some of these patients.

BACKGROUND: This is the first report of human exposure to the novel compound follicle stimulating hormone (FSH)-C-terminal peptide (CTP) 'FSH-CTP' (Org 36286), a long-acting recombinant FSH like substance, consisting of the alpha-subunit of human FSH and a hybrid beta-subunit. The latter is composed of the beta-subunit of human FSH and the C-terminus part (CTP) of the beta-subunit of human chorionic gonadotrophin (HCG). METHODS: In this phase I, non-blind, multi-centre study, 13 hypogonadotrophic hypogonadal male subjects were enrolled to test the safety of FSH-CTP in terms of antibody formation in humans. Furthermore, the pharmacokinetic profile of this new compound was determined. Subjects were injected four times with 15 microg FSH-CTP with an interval of approximately 4 weeks between each injection. RESULTS: No drug related (serious) adverse events occurred. No antibodies against FSH-CTP or chinese hamster ovary (CHO)-cell derived proteins were detected and measurement of local tolerance demonstrated that s.c. administration of FSH-CTP is well tolerated and no increase in intensity of injection-site responses was observed after repeated exposure to FSH-CTP. After the first and third injection, FSH-CTP serum concentrations were determined. Overall mean (+/- SD) C(max) was 0.426 (+/- 0.116) ng/ml, mean t(1/2) and AUC(0-infinity) were 94.7 (+/- 26.2) h and 81.5 (+/- 18.8) ng.h/ml respectively. Compared with recFSH (Puregon), the half life of FSH-CTP was increased 2-3 times. Following the first and third injection a clear rise in serum inhibin-B concentrations were observed. CONCLUSIONS: The use of FSH-CTP is safe and does not lead to detectable formation of antibodies. Furthermore, the pharmacokinetic and dynamic profile of FSH-CTP may lead to the development of new, more convenient regimens for the treatment of male and female infertility.

We present a rare case in which therapy of primary ovarian pregnancy, using laparoscopic laser surgery (videolaseroscopy), was successfully performed without the need of laparotomy. Because operative laparoscopy has the benefits of reduced morbidity, reduced hospitalization and rapid recovery, and because it has the advantage of reducing postoperative adhesions as compared to laparotomy, it is the preferable technique for treatment of ovarian gestation after a laparoscopic diagnosis, especially for a woman who desires to preserve her fertility potential.

The basic foundation for normal puberty and adult reproductive function is established during fetal life with the adequate development of the hypothalamus, pituitary and gonads. Further maturation and differentiation of the hypothalamic-pituitary-gonadal axis continues throughout childhood, puberty, adult life and senescence. Pituitary FSH and LH play a central role in the cascade of events in the hypothalamic-pituitary-gonadal axis by mediating between the brain and hypothalamus on one hand and the end-organ, the ovary, on the other. Absent or low pituitary secretion of FSH and LH, as occurs in hypothalamic/pituitary hypogonadism, leads in women to anovulation, amenorrhoea and absent ovarian follicular development. The ability of gonadotrophins to modulate ovarian function depends on their rate of synthesis by the pituitary gonadotrophs, on their circulating concentrations (which vary throughout life and throughout the menstrual cycle), on the relative abundance of the multiple forms of gonadotrophins that have varying biological activity, on the presence of their receptors on the different cell types of the ovary, on the intracellular adenylate cyclase enzyme that causes the production of cAMP, and on the extra- and intragonadal factors that are able to modulate the effects of gonadotrophins in the ovary. Recent clinical and basic research with recombinant gonadotrophins, molecular biological studies on the localization, function and regulation of the long sought after gonadotrophin receptors, as well as research on the interaction between gonadotrophins and local intragonadal factors have widened our knowledge about the function and role of FSH and LH in the ovary and have provided new insights into previously unanswered questions of ovarian physiology and pathophysiology and will provide the basis for the design of new treatment strategies to overcome ovulatory gonadotrophin-dependent dysfunction in the future.

We present our experience with 60 trials of external cephalic version under tocolysis (EVT) performed on 58 women with uncomplicated (low-risk) pregnancies at term (37 to 42 weeks) during a 10-month period. Version was successful in 67.2% of the subjects (70.7% of trials). Fetal well-being was monitored before, during and after the procedure by cardiotocography and real-time ultrasound (RTUS). No analgetic or anesthetic medication was administered. Transient fetal bradycardia was recorded in 18 women. No major complications were noted. Compared with the period preceding the protocol, the breech rate declined during the study period by 1.02% (P less than 0.02) with a parallel decline of 1.12% (P less than 0.001) in the low-risk breech group affected by the protocol. The cesarean section rate for low-risk breeches fell from 1.85 to 0.89% (P less than 0.001), while the overall cesarean section rate decreased from 10.15 to 9.1% (not significant). We conclude from our experience and previous studies that EVT/RTUS is a reasonable alternative in the management of pathological presentations near term, provided that only low-risk pregnancies are included, and analgesia or anesthesia for external version under tocolysis is avoided.

Internal podalic version of the second twin in transverse lie has usually been performed after first rupturing the membranes of the second amniotic sac. In a prospective study on internal podalic version with unruptured amniotic membranes, 11 second-born twins in transverse lie were successfully delivered, with good neonatal outcome and without birth injuries. From our experience, it appears that this modified technique, when used within the presented guidelines, offers a reasonable alternative for the safe delivery of the second twin.

Ciliary ultrastructure was studied and quantitatively estimated in a 27-year-old sterile woman suffering from complete KS. Ciliated epithelium was obtained from both nasal mucosa and a fallopian tube. Cilia from both locations were devoid of DA. Various MT abnormalities were found in 16 percent of respiratory epithelial and 21 percent of fallopian tube ciliary cross-sections. The abnormality related to radial spoke defect was frequently seen. The findings in the fallopian tubes were compared to three normal control cases. In these, DA were visible, and MT defects were mainly of excess or missing microtubules. The relevance of these findings to fertility is not clear.