The curious case of premature luteinization.

PURPOSE: Premature luteinization (PL) affects 12.3-46.7% of fresh in vitro fertilization cycles, and there is accumulating evidence confirming its negative effect on success rates. However, despite its clinical significance, PL is poorly understood and defined. This narrative review aims to provide a fresh look at the phenomenon of PL by summarizing the existing evidence and re-evaluating fundamental issues. METHODS: A thorough electronic search was conducted covering the period from 1978 until January 2018 in PubMed, Embase, and Medline databases, and references of relevant studies were cross-checked. Meeting proceedings of the European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine were also hand searched. RESULTS: In the curious case of PL, one should go back to the beginning and re-consider every step of the way. The pathogenesis, definition, measurement methods, clinical implications, and management strategies are discussed in detail, highlighting controversies and offering "food for thought" for future directions. CONCLUSIONS: Authors need to speak the same language when studying PL in order to facilitate comparisons. The terminology, progesterone cut-off, measurement methods and days of measurement should be standardized and globally accepted; otherwise, there can be no scientific dialog. Future research should focus on specific patient profiles that may require a tailored approach. Progesterone measurements throughout the follicular phase possibly depict the progesterone exposure better than an isolated measurement on the day of hCG. Adequately powered randomized controlled trials should confirm which the best prevention and management plan of PL is, before introducing any strategy into clinical practice.

Intertwin estimated fetal weight or crown rump length discordance and adverse perinatal outcome.

AIM: In the current review study, we present recent data regarding the importance of intertwin estimated fetal weight (EFW) and crown rump length (CRL) discordance for the prediction of adverse perinatal outcome both in monochorionic and in dichorionic diamniotic gestations. RESULTS: Twins with significant weight disparity are associated with higher rates of perinatal morbidity and mortality, regardless of gestational age at delivery. However, there is no agreement regarding as to the cut off value above which the perinatal outcome is unfavorably affected and the threshold range from 10 to 30%. On the other hand, CRL discrepancy has proved to be a weak predictor of adverse outcomes, such as fetal or neonatal death in fetuses without chromosomal and structural abnormalities. In clinical practice, decisions about obstetric surveillance of discordant twin gestations, frequency of fetal sonographic monitoring and time of delivery are usually based on amniotic fluid volume and Doppler assessments on a weekly basis. CONCLUSION: Significant EFW discordance leads to adverse perinatal outcome, although the cut-off value has not yet been estimated. CRL discrepancy is not correlated well with adverse perinatal outcome. However, increased monitoring of women with EFW and CRL discrepancy is suggested.

Spontaneous uterine rupture in a primigravid woman in the early third trimester attributed to adenomyosis: a case report and review of the literature.

We report a rare case of spontaneous uterine rupture of an unscarred uterus caused by adenomyosis in the early third trimester. A 33-year-old primigravid woman was referred to our department because of severe acute abdominal pain and signs and symptoms of hemorrhagic shock. Ultrasound exanimation performed at admission revealed a living, intrauterine fetus of 28 weeks gestational age with reduced amniotic fluid and presence of free peritoneal fluid. The fetal heart rate was non-reassuring with variable decelerations and severe fetal bradycardia. Emergency cesarean section revealed massive hemoperitoneum and complete rupture in the uterine fundus. Subtotal peripartum hysterectomy with conservation of adnexae was performed. Histological examination revealed adenomyosis at the site of uterine rupture.

Association of estrogen receptor alpha (ERα) gene polymorphisms with endometrial thickness and lipid profile in women with breast cancer treated with aromatase inhibitors.

Aromatase inhibitors (AIs) provide an alternative to tamoxifen as an adjuvant therapy for post-menopausal, hormone-receptor positive breast cancer patients. The aim of the present study was to evaluate the effect of PvuII and XbaI polymorphisms of the ERα gene at ΑΙs treatment's adverse effects in post-menopausal women with breast cancer. The study included 87 post-menopausal women with ER-positive breast cancer treated with AIs and 80 healthy controls. The overall presence of ERα polymorphisms in all women with breast cancer was not different from the healthy controls. Endometrial thickness under AIs treatment was reduced from (mean value ± SD) 6,404 ± 2,901 mm to 3,666 ± 1,4656 mm. Moreover, the AA XbaI genotype was associated with greater reduction in endometrial thickness during therapy with AIs (p = 0.005). The presence of the CC PvuII and the AA XbaI genotypes were associated with elevated LDL levels and elevated triglycerides. In conclusion, the results of the present study showed that the genotype of women with breast cancer under AIs treatment might influence treatment's adverse effects, as, the presence of the CC PvuII and the AA XbaI genotypes of the ERα were associated with elevated LDL and triglycerides serum levels, while the AA XbaI genotype was associated with a greater reduction in endometrial thickness.

Prediction of respiratory failure in late-preterm infants with respiratory distress at birth.

The aim of this study was to evaluate indices of respiratory failure in terms of their ability to predict respiratory impairment and need for ventilatory support in late-preterm neonates with respiratory distress. Arterial blood gas data during the first 12 postnatal hours or until intubation were recorded in 155 neonates with gestational age 34(0/7)-36(6/7) weeks admitted in the NICU with respiratory distress between January 2006 and June 2008. Alveolar-arterial oxygen tension difference (A-aDO(2)), arterial to alveolar oxygen tension ratio (a/A ratio), and partial arterial oxygen tension to inspired oxygen fraction ratio (PaO(2)/FiO(2)) were calculated. Considering the worst single value of each parameter, receiver operating characteristic curve analyses and area under the curve (AUC) comparisons were used to evaluate their predictive performance. Fifty-five neonates (35.5%) required mechanical ventilation. The predictive performances of the maximum A-aDO(2) (AUC 0.97), minimum a/A ratio (AUC 0.95), and minimum PaO(2)/FiO(2) (AUC 0.95) were similar. The A-aDO(2) at a threshold of >200 mmHg proved to be more effective than the other parameters, having excellent positive and negative likelihood ratios of 24.5 and 0.02, respectively. This threshold was achieved by 98.25% of the neonates who developed respiratory failure at a median of 3 h before the ventilatory support to be definitely decided. Composite indices, such as A-aDO(2), a/A ratio, and PaO(2)/FiO(2), can reasonably predict respiratory failure in late-preterm neonates with respiratory distress, allowing for closer monitoring, early medical intervention, or transfer to a level III neonatal unit.

The impact of oral contraceptives and metformin on anti-Müllerian hormone serum levels in women with polycystic ovary syndrome and biochemical hyperandrogenemia.

OBJECTIVE: To assess the impact of metformin and of two different oral contraceptives (OCs) containing cyproterone acetate and drospirenone, on serum anti-Müllerian hormone (AMH) levels, in a cohort of women with polycystic ovary syndrome (PCOS) with hyperandrogenism. DESIGN: Prospective randomised study. SETTING: Division of Endocrinology and Human Reproduction, Aristotle University of Thessaloniki. PATIENTS: Forty-five (45) women with PCOS diagnosed according to the criteria proposed in 1990 by the NIH. INTERVENTIONS: Women with PCOS were randomised into three groups, all treated for 6 months: Group A received an OC containing 35 µg ethinylestradiol plus 2 mg cyproterone acetate, Group B received an OC containing 30 µg ethinylestradiol plus 3 mg drospirenone and Group C received metformin 850 mg × 2. Main outcome measure(s). Anti-Müllerian hormone levels were measured by a specific ELISA. RESULTS: AMH was significantly decreased under treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate (p = 0.002 at 3 months and p < 0.001 at 6 months). Treatment with 30 µg ethinylestradiol plus 3 mg drospirenone, and treatment with metformin 850 mg × 2 did not significantly affect serum AMH levels. AMH was significantly decreased under OCs treatment compared to metformin 850 mg × 2 (p = 0.005). CONCLUSION(S): AMH serum levels were significantly decreased under treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate, due to decrease in androgens and suppression of gonadotropins.

Increased plasma viscosity in young women with polycystic ovary syndrome using an oral contraceptive containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate.

OBJECTIVES: To investigate the influence of 6 months of treatment with an oral contraceptive (OC) containing 35 µ g ethinyl estradiol and 2 mg cyproterone acetate on plasma viscosity (PV) in young women with polycystic ovary syndrome (PCOS). DESIGN: Patients with PCOS were assessed for PV before and after 6 months of treatment with an OC containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate. PV was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C. SETTINGS: Subjects were recruited from the Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology at the University Hospital of Patras, Greece. PATIENTS: The study included 66 young women with PCOS. MAIN OUTCOME MEASURES: PV. RESULTS: In PCOS women as a whole, PV at baseline was 1.249 ± 0.049 mm(2)/s (n = 66). After 6 months of treatment with an OC containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate, PV was increased to 1.268 ± 0.065 mm(2)/s (p = 0.038). The difference between PV before and after 6 months of treatment with an OC containing 35 µg ethinyl estradiol and 2 mg cyproterone acetate (Δviscosity) was 0.01864 ± 0.071452 mm(2)/s. ΔViscosity was related to ?fibrinogen (r = 0.270, p = 0.046), to Δhematocrit (r = 0.514, p = 0.09) and to Δtriglycerides (r = 0.292, p = 0.021). CONCLUSION: Young women with PCOS presented an increased PV under OC treatment with 35 µg ethinyl estradiol and 2 mg cyproterone acetate.

The importance of venous Doppler velocimetry for evaluation of intrauterine growth restriction.

The management of growth-restricted fetuses requires accurate diagnosis to optimize the timing of delivery. Doppler velocimetry is the only noninvasive method for assessing the fetoplacental hemodynamic status. This review will give a critical overview of the current knowledge on fetal venous blood flow in pregnancies complicated by in-trauterine growth-restricted fetuses. Adaptation of the circulation in intrauterine growth-restricted fetuses is described. Normal and abnormal venous Doppler waveforms are presented. Correlations of abnormal waveforms with the presence of acidemia and perinatal outcomes are emphasized. Limitations of venous Doppler velocimetry for optimizing the time for delivery and the perinatal outcome are also presented.

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia.

PURPOSE: The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. METHODS: The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR-restriction fragment length polymorphism (RLFP) assay. RESULTS: No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. CONCLUSION: The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

Feto-maternal risks associated with pregnancy achieved through oocyte donation in a woman with Turner syndrome.

We report a case of a 40-year-old primipara Caucasian woman with Turner syndrome (TS) and Hashimoto thyroiditis who had underwent a successful IVF-ET cycle with oocyte donation and single embryo transfer. All pregnancies in women with TS are considered as high risk, with cardiovascular complications being the most dangerous. Our case represents a typical case of fetal growth restriction with gradual slowing down of fetal growth after 28 weeks. At 37 + 3 gestational weeks, a healthy male newborn weighing 2240 g, with artery pH of 7.32 was delivered by cesarean section. The neonate was small for gestational age. Women with TS who become pregnant need close surveillance from a multidisciplinary team of cardiologists, obstetricians and endocrinologists. The primary goal is to prevent maternal complications and to improve perinatal outcome. In doing so, a thorough evaluation of fetal growth and uteroplacental and fetal circulation should by no means be omitted, after 26-28 weeks of gestation. The examinations should be at monthly or even shorter intervals to find early signs of growth restriction and act accordingly.

Obesity and insulin resistance increase plasma viscosity in young women with polycystic ovary syndrome.

OBJECTIVE: To investigate the plasma viscosity in young women with polycystic ovary syndrome (PCOS). DESIGN: Patients with PCOS and healthy controls were assessed for plasma viscosity. The acquired data were tested for association with hyperandrogenemia, obesity and insulin resistance (IR) in patients with PCOS. Plasma viscosity was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37 degrees C. PATIENTS: The study included 96 young women with PCOS and 72 healthy controls. Main outcome measures. Plasma viscosity and IR. RESULTS: Plasma viscosity was 1.243 +/- 0.67 mm(2)/s in the control group and 1.252 +/- 0.82 in women with PCOS (p = 0.416). Using multiple regression analysis, total protein (B = 0.348, p = 0.005), area under curve for insulin (B = 0.320, p = 0.011) and BMI (B = 0.315, p = 0.013) were proven to be significantly correlated to plasma viscosity. Plasma viscosity was significantly increased in women with PCOS with IR compared to matched for age and BMI PCOS women without IR (1.300 +/- 0.055 vs. 1.231 +/- 0.049 mm(2)/s) (p = 0.004). CONCLUSION: Young women with PCOS presented a plasma viscosity that was increased by obesity and IR. Therefore, clinical management of young overweight women with PCOS with IR should always include a serious reduction in body weight and the use of oral contraceptive treatment with cautious.

Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency.

PURPOSE: Previous studies have suggested that deletion of Foxo3a, FoxL2, PTEN, p27, and AMH leads to early exhaustion of the primordial follicle pool and premature ovarian insufficiency (POI) in transgenic mice. Our aim was to assess for the first time, to our knowledge, messenger RNA (mRNA) expression of these genes and AMHR2 in human ovarian tissue from women with POI. We hypothesized that these genes would be underexpressed in POI women compared with healthy controls. METHODS: mRNA levels were evaluated by quantitative reverse transcription-polymerase chain reaction and real-time polymerase chain reaction in cortical ovarian tissue obtained by laparoscopy from Caucasian Greek women with POI (n = 5) and healthy women with normal menstruation (n = 6). Morphological analysis of the ovarian biopsies was also performed to assess the presence of primordial or other types of growing follicles. RESULTS: Ovarian tissue from POI patients showed lower Foxo3a, FoxL2, and p27 mRNA expression compared with controls (p = 0.017, p = 0.017, and p = 0.030, respectively). mRNA expression of AMH, PTEN, and AMHR2 was reduced in ovarian biopsies from POI patients as well. However, these differences were not statistically significant (p = 0.143, p = 0.247, and p = 0.662, respectively). Morphological analysis showed complete lack of follicular structures in all POI biopsies. CONCLUSIONS: Our findings suggest a possible role of Foxo3a, FoxL2, and p27 in the pathogenesis of human POI, which may prove to be of great diagnostic-therapeutic value. Further larger studies are needed to identify a similar pattern for AMH, PTEN, and AMHR2 and to investigate gene expression at a protein level.

Correction to: Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency.

The original version of this article, published 21 October 2019, unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.

Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25-29 years to 5.1% for women aged 50-60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25-29) to 76.3% (for women 40-49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

Increased frequency of thyroid nodules and breast fibroadenomas in women with uterine fibroids.

Fibroids or leiomyomas or myomas of the uterus are the most common benign gynecologic disease, while fibroadenomas of the breast are most frequently seen in young women, usually within 20 years after puberty. Multiple tumors in one or both breasts are found in 10-15% of patients. Single thyroid nodules are much more common in women than in men, and their prevalence increases with age. The aim of the present study was to determine cross-sectionally the incidence of solitary thyroid nodules and fibroadenomas of the breast in women with uterine fibroids. In women with uterine adenomas, the frequency of fibroadenomas of the breast was 65% and of thyroid nodules was 38.7%, while in women with a normal uterus, the frequency was 35% and 20%, respectively. Therefore, women with uterine fibroids have an increased incidence of thyroid nodules (t = 4.68, p = 0.030) and of fibroadenomas of the breast (t = 11.74, p = 0.001).

Vibroacoustic stimulation in abnormal biophysical profile: verification of facilitation of fetal well-being.

OBJECTIVES: To verify the effect of vibroacoustic stimulation on biophysical profile score, with a prospective randomised study. STUDY DESIGN: All women with singleton pregnancy, gestational age >or=30 weeks, intact membranes and biophysical profile score

Second trimester amniotic fluid endothelin-1 concentrations and subsequent development of intrauterine growth restriction.

OBJECTIVE: The purpose of this prospective study was to record endothelin-1 (ET-1) concentrations in the second trimester amniotic fluid and compare these values in women who developed intrauterine growth restriction (IUGR) later in pregnancy with those with uneventful pregnancies. METHOD: Amniotic fluid was retrieved by amniocentesis from 125 women in the second trimester of pregnancy. The levels of ET1 were measured by a sensitive and specific radioimmunoassay. RESULTS: From the 125 women included in the study 12 had pregnancies that later developed IUGR and 88 had uneventful pregnancies. The ET1 concentration was significantly higher (P<0.005) in women who later developed IUGR than in normal pregnancy (106 pg/ml versus 64.7 pg/ml). CONCLUSION: The amniotic fluid concentration of ET1 is elevated by the second trimester in women who later develop IUGR.

The Impact of Adenomyosis on Women's Fertility.

Until recently, adenomyosis has been associated with multiparity, not impaired fertility. Currently, adenomyosis is diagnosed with increasing frequency in infertile patients since women delay their first pregnancy until their late 30s or early 40s. Although an association between adenomyosis and infertility has not been fully established, based on the available information, recent studies suggested that adenomyosis has a negative impact on female fertility. Several uncontrolled studies with limited data also suggested that treatment of adenomyosis may improve fertility. This article discusses (i) the hypothesis and epidemiology of adenomyosis, (ii) diagnostic techniques, (iii) clinical evidence of correlation between adenomyosis and infertility, (iv) proposed mechanism of infertility in women with adenomyosis, (v) different treatment strategies and reproductive outcomes, and (vi) assisted reproductive technology outcome in women with adenomyosis.

Late or emergency (salvage) cerclage of a dilated cervix after tissue support with Pelvicol implant: a case.

Our objective was to evaluate the effectiveness of a late or emergency (salvage) cerclage after tissue reinforcement with Pelvicol natural implant, in preventing premature rupture of the fetal membranes and advancing pregnancy prolongation. A flat sheet of Pelvicol, a sterile acellular natural (porcine) implant was used in an emergency cerclage to reinforce the thin tissues of a widely dilated cervix in a 24 weeks' twin gestation with prolapsed unruptured membranes, without contractions, placental abruption, or intrauterine infection. The gestation was extended to 38 weeks without any complications. Two live healthy newborns were delivered by elective cesarean section due to a nonvertex/vertex presentation. The implant was found to be attached almost unaltered firmly on the outer surface of the membrane sac just opposite to the internal os. It seems that Pelvicol is safe and apparently protects by clothing the thinned, soft, and weak wall of a significantly dilated uterine cervix and the bulging or protruding gestational membranes. It also reinforces and strengthens the tissue thickness and resistance, rendering more accurate and safe the otherwise delicate and risky late cerclage. The technique gives hopes that it can help in pregnancy prolongation.