Factors associated with female infertility in Ukraine: results a multicenter study.

OBJECTIVE: Aim: To determine the current prevalence of female infertility and characterize and identify risk factors associated with infertility in Ukraine. PATIENTS AND METHODS: Materials and Methods: Multicenter prospective cohort study was conducted from January 2021 to December 2023 in twelve medical centers from nine regions of Ukraine. Definitions of infertility were adapted from the World Health Organization. According to the data collected from questionnaire, participants were divided into infertile and fertile groups and analyzed associated factors. RESULTS: Results: Among all the 7,618 participants in this study, the prevalence of female infertility was 24.3%. The prevalence of primary infertility was 5.9%, and the prevalence of secondary infertility was 18.4%. In logistic multivariate regression analyses, female infertility was associated with age of women (p<0.001), age of first sexual intercourse (p<0.001), history of gynecological surgery (p<0.001), marital status (p<0.001), age of marriage (p<0.001), decreased ovarian reserve (DOR) (p=0.006), family history of infertility (p<0.001), history of cervicitis (p=0.007), history of surgical abortion (p<0.001), history of endometritis (p=0.027), bacterial vaginosis (p=0.023), and aerobic vaginitis (< 0.001). CONCLUSION: Conclusions: Our data suggest a high prevalence of female infertility in Ukraine. The prevalence of secondary infertility was higher than primary infertility. Age of women, age of first sexual intercourse, history of gynecological surgery, marital status, age of marriage, DOR, family history of infertility, history of cervicitis, history of surgical abortion, history of endometritis, bacterial vaginosis, and aerobic vaginitis were associated with infertility.

Melatonin 1A and 1B Receptors' Expression Decreases in the Placenta of Women with Fetal Growth Restriction.

Melatonin and its metabolites prevent oxidative stress and apoptosis, and it is actively produced by the placenta during pregnancy. Melatonin 1A and 1B receptors are present in human villous trophoblastic cells. We aimed to investigate the expression of melatonin 1A and 1B receptors in human placental tissue in the case of placental insufficiency manifested as the intrauterine growth restriction syndrome of the fetus (IUGR). Thirty-two pregnant women aged 18-36 with placental insufficiency manifested at the term 36 weeks of gestation as the IUGR syndrome (the estimated fetal weight less than the 3rd percentile) were included in the experimental group; all their babies had the diagnosis confirmed at birth, which occurred after 37 weeks of gestation. The control group consisted of 30 women with uncomplicated pregnancy of the same term. Pieces of the placental tissue were obtained after deliveries, and melatonin 1A and 1B receptors were immunoassayed; the richness of melatonin receptors in the placental tissue was estimated on the basis of immunohistochemical (IHC) staining of receptors, calculated in the IHC image score. The optical density of melatonin 1A receptors in the placentas obtained from women whose pregnancies were complicated with IUGR was significantly lower than that in the placentas from uncomplicated pregnancies: generally in the trophoblast, it was 0.095 ± 0.0009 IHC image score (in the control group, 0.194 ± 0.0015, p < 0.0001); in the apical parts of the syncytiotrophoblast, 0.108 ± 0.0016 IHC image score (in the control group, 0.221 ± 0.0013, p < 0.0001); and in the stromal cells of placental villi, 0.112 ± 0.0013 IHC image score (in the control group, 0.156 ± 0.0011, p < 0.0001). The optical density of melatonin 1B receptors in placentas obtained from women whose pregnancies were complicated with IUGR was also lower than that in the placentas from uncomplicated pregnancies: generally in the trophoblast, it was 0.165 ± 0.0019 IHC image score (in the control group, 0.231 ± 0.0013, p < 0.0001), and in the apical parts of the syncytiotrophoblast, 0.188 ± 0.0028 IHC image score (in the control group, 0.252 ± 0.0009, p < 0.0001). There was no difference found in the optical density of melatonin 1B receptors in the stromal cells of placental villi between the two groups: in the experimental group, 0.109 ± 0.006 IHC image score, and in the control group, 0.114 ± 0.0011 (p = 0.65). Melatonin receptors 1A and 1B are significantly less expressed in the placental tissue in the case that pregnancy is complicated with placental insufficiency, manifested as the intrauterine growth restriction syndrome of the fetus.

Early pregnancy and endothelial dysfunction.

OBJECTIVE: The aim is to analyze the value of endothelial dysfunction markers during pregnancy. PATIENTS AND METHODS: Materials and methods: We have examined 153 pregnant women to identify endothelial dysfunction markers of endothelin-1, nitrogen oxide (NO) that have been studiedusing immunoenzymometric sets for an uncomplicated and complicated pregnancy. RESULTS: Results: We found that the concentration of endothelin-1 repeatedly exceeded the rates in pregnant women with miscarriages than during physiological pregnancy. The diametrically opposite pattern concerns the level of nitrogen oxide. These changes in the markers of the functional state of the endothelin indicate the development of the dysfunction of this system in women with the pathology of pregnancy. CONCLUSION: Conclusions: Consequently, endothelial dysfunction can be considered to be one of the reasons for miscarriage in the examined women. Therefore, the definition of markersof endothelial dysfunction has prognostic value.

17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial.

BACKGROUND: Women with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or "17P") to placebo has been published, and this trial was stopped early due to a large treatment benefit. OBJECTIVE: This study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. STUDY DESIGN: This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%-11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. RESULTS: Baseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71-1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68-1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4-1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. CONCLUSION: In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.