Spontaneous and iatrogenic ovarian hyperstimulation syndrome in the absence of FSHR mutations: a case report of two unexpected cases.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a complication of controlled ovarian hyperstimulation (COH). It is a potentially life-threatening condition that usually occurs either after human chorionic gonadotropins (hCG) administration in susceptible patients or as a result of an implanting pregnancy, regardless of whether it was achieved by natural conception or infertility treatments. Despite many years of clinical experience regarding the adoption of preventive measures and the identification of patients at high risk, the pathophysiology of OHSS is poorly understood and no reliable predictive risk factors have been identified. CASES PRESENTATION: We report about two unexpected cases of OHSS following infertility treatments, occurring after freeze-all strategy with embryo cryopreservation approaches. The first case developed spontaneous OHSS (sOHSS), despite efforts to prevent its manifestation by a segmentation approach, including frozen embryo replacement cycle. The second case developed a late form of iatrogenic OHSS (iOHSS), even though the absence of any risk factors. No mutations in the follicle-stimulating hormone (FSH) receptor (FSHR)-encoding gene were detected, suggesting that the high levels of hCG due to the twin implanting pregnancies could be the only triggering factor of OHSS outbreak. CONCLUSION: Freeze-all strategy with embryo cryopreservation cannot entirely prevent the development of OHSS, which may occur in its spontaneous form independently from the FSHR genotype. Although OHSS remains a rare event, all infertile patients requiring ovulation induction or controlled ovarian stimulation (COS) may be at potential risk of OHSS, either in the presence or in the absence of risk factors. We suggest closely monitoring cases of pregnancy following infertility treatments in order to provide early diagnosis and adopt the conservative management.

Is endometrial receptivity impaired in women with polycystic ovary syndrome?

Women with polycystic ovary syndrome (PCOS) seem to have impaired reproductive performances. It is generally considered that an altered ovulatory function is the main cause of infertility in the affected women. However, other factors may play a role in the pathogenesis of the PCOS-related infertility. During the last years, more and more importance has been given to endometrium as contributor of the PCOS-related subfertility. In the present narrative review, the main and recent experimental and clinical data will discuss in order to clarify the role played by the endometrium in the PCOS-related subfertility. The overall analysis of available data suggests that, in women with PCOS, the endometrium is primarily affected, and closely and deeply influenced by the several hormonal, metabolic, clinical alterations related to the syndrome.

Are sperm parameters able to predict the success of assisted reproductive technology? A retrospective analysis of over 22,000 assisted reproductive technology cycles.

BACKGROUND: An explosive increase in couples attending assisted reproductive technology has been recently observed, despite an overall success rate of about 20%-30%. Considering the assisted reproductive technology-related economic and psycho-social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of assisted reproductive technology success, male parameters are largely underestimated so far. STUDY DESIGN: Retrospective, observational study. OBJECTIVES: To evaluate whether conventional semen parameters could predict assisted reproductive technology success. MATERIALS AND METHODS: All couples attending a single third-level fertility center from 1992 to 2020 were retrospectively enrolled, collecting all semen and assisted reproductive technology parameters of fresh cycles. Fertilization rate was the primary end-point, representing a parameter immediately dependent on male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to the World Health Organization manual editions used for semen analysis. RESULTS: Note that, 22,013 in vitro fertilization and intracytoplasmic sperm injection cycles were considered. Overall, fertilization rate was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective of the World Health Organization manual edition. In the in vitro fertilization setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted the fertilization rate (statistical accuracy = 71.1%). Sperm motilities also predicted pregnancy (p < 0.001) and live birth (p = 0.001) rates. In intracytoplasmic sperm injection cycles, sperm morphology predicted fertilization rate (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p < 0.001) and live birth (p < 0.001) rates and a cut-off of 5.5% was identified as a threshold to predict clinical pregnancy (area under the curve = 0.811, p < 0.001). DISCUSSION: Interestingly, sperm motility plays a role in predicting in vitro fertilization success, while sperm morphology is the relevant parameter in intracytoplasmic sperm injection cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples.

How Can We Treat Vulvar Carcinoma in Pregnancy? A Systematic Review of the Literature.

According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17-41 years). The tumor size range was 0.3-15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5-48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

Sphingosine-1 phosphate induces cAMP/PKA-independent phosphorylation of the cAMP response element-binding protein (CREB) in granulosa cells.

BACKGROUND AND AIMS: Sphingosine-1 phosphate (S1P) is a lysosphingolipid present in the ovarian follicular fluid. The role of the lysosphingolipid in gonads of the female is widely unclear. At nanomolar concentrations, S1P binds and activates five specific G protein-coupled receptors (GPCRs), known as S1P1-5, modulating different signaling pathways. S1P1 and S1P3 are highly expressed in human primary granulosa lutein cells (hGLC), as well as in the immortalized human primary granulosa cell line hGL5. In this study, we evaluated the signaling cascade activated by S1P and its synthetic analogues in hGLC and hGL5 cells, exploring the biological relevance of S1PR-stimulation in this context. METHODS AND RESULTS: hGLC and hGL5 cells were treated with a fixed dose (0.1 µM) of S1P, or by S1P1- and S1P3-specific agonists SEW2871 and CYM5541. In granulosa cells, S1P and, at a lesser extent, SEW2871 and CYM5541, potently induced CREB phosphorylation. No cAMP production was detected and pCREB activation occurred even in the presence of the PKA inhibitor H-89. Moreover, S1P-dependent CREB phosphorylation was dampened by the mitogen-activate protein kinase (MEK) inhibitor U0126 and by the L-type Ca2+ channel blocker verapamil. The complete inhibition of CREB phosphorylation occurred by blocking either S1P2 or S1P3 with the specific receptor antagonists JTE-013 and TY52156, or under PLC/PI3K depletion. S1P-dependent CREB phosphorylation induced FOXO1 and the EGF-like epiregulin-encoding gene (EREG), confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. However, S1P or agonists did not modulate granulosa cell viability and proliferation in our conditions. CONCLUSIONS: This study demonstrates for the first time that S1P may induce a cAMP-independent activation of pCREB in granulosa cells, although this is not sufficient to induce intracellular steroidogenic signals and progesterone synthesis. S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P-S1PR axis may cooperate with gonadotropins in modulating follicle development.

Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival.

Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with preferential Gαs protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromers triggered anti-apoptotic/proliferative FSH signaling delivered via the Gßγ dimer, whereas impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation.

Two human menopausal gonadotrophin (hMG) preparations display different early signaling in vitro.

Commercial hMG drugs are marketed for the treatment of infertility and consist of highly purified hormones acting on receptors expressed in target gonadal cells. Menopur® and Meriofert® are combined preparation of FSH and hCG and are compared in vitro herein. To this purpose, the molecular composition of the two drugs was analyzed by immunoassay. The formation of FSH receptor and LH/hCG receptor (FSHR; LHCGR) heteromer, intracellular Ca2+ and cAMP activation, ß-arrestin 2 recruitment and the synthesis of progesterone and estradiol were evaluated in transfected HEK293 and human primary granulosa lutein cells treated by drugs administered within the pg-mg/ml concentration range. Molecular characterization revealed that Meriofert® has a higher FSH:hCG ratio than Menopur® which, in turn, displays the presence of LH molecules. While both drugs induced similar FSHR-LHCGR heteromeric formations and intracellular Ca2+ increase, Meriofert® had a higher potency than Menopur® in inducing a cAMP increase. Moreover, Meriofert® revealed a higher potency than Menopur® in recruiting ß-arrestin 2, likely due to different FSH content modulating the tridimensional structure of FSHR-LHCGR-ß-arrestin 2 complexes, as evidenced by a decrease in bioluminescence resonance energy transfer signal. This drug-specific activation of intracellular signaling pathways is consistent with the molecular composition of these preparations and impacts downstream progesterone and estradiol production, with Menopur® more potent than Meriofert® in inducing the synthesis of both the steroids. These findings are suggestive of distinct in-vivo activities of these preparations, but require cautious interpretation and further validation from clinical studies.

Uterine transplantation and IVF for congenital or acquired uterine factor infertility: A systematic review of safety and efficacy outcomes in the first 52 recipients.

Uterine transplantation (UTx) associated with IVF restores fertility in women affected by absolute uterine factor infertility (AUFI). Pregnancies achieved both in women undergoing any solid organ transplantation and following IVF are associated with an increased risk of maternal and neonatal complications. This systematic review evaluated this risk in UTx-IVF treated women focusing on the safety and efficacy features of the treatment. Twenty-two studies and three press releases reporting on 52 UTx-IVF treatments were identified. Regarding the safety of treatment, 38/52 (73,1%) of surgical procedures led to the restoration of uterine function in recipients, 12/52 (23,1%) of recipients experienced post-operative complications requiring hysterectomy, and 2/52 (3,8%) of procedures failed before uterine recipients' surgery due to intra-operative complications. Regarding the efficacy of treatment, results focused on transplanted patients showing full recovery of organ functioning: 16/38 (42,1%) of patients achieved a pregnancy, including two women who gave births twice. UTx-IVF pregnancies led to 16 deliveries and all new-borns were healthy. Six out of 16 (37,5%) UTx pregnancies faced major complications during gestation. Preterm births occurred in 10/16 (62,5%) UTx deliveries. Our data indicates that the risk of gestational and delivery complications deserves important consideration in AUFI women receiving UTx-IVF treatments. However, these observations are preliminary and need to be revised after larger series of data are published.

A monocentric analysis of the efficacy of extracellular cryoprotectants in unfrozen solutions for cleavage stage embryos.

BACKGROUND: In the absence of international guidelines indicating the usage of vitrification rather than slow-freezing, the study aim was to analyze a large cohort of slow-frozen/thawed embryos to produce a rationale supporting the standardization of IVF cryopreservation policy. METHODS: This retrospective analysis included 4779 cleavage stage embryos cryopreserved by slow-freezing/thawing from September 2009 to April 2017 at a single Center. Biological and clinical outcomes of three different commercial kits adopted sequentially, i.e. Vitrolife Cleave Kit® from Vitrolife (kit 1) vs. K-SICS-5000 Kit® and K-SITS-5000 Kit® from Cook Medical (kit 2) and Freeze/Thaw 1™ Kit® from Vitrolife (kit 3) were collected and compared in the light of cryoprotectants composition. RESULTS: Kit 3 compared to kit 1 and kit 2 showed significantly (P < 0.001) higher embryo survival (79.9% vs. 75.6 and 68.1%, respectively) and frozen embryo replacement (91.5% vs. 86.5 and 83.3%, respectively) rates, and significantly (P < 0.001) lower blastomere degeneration rate (41.5% vs. 43.6 and 52.4%, respectively). No significant difference for clinical outcomes was observed among kits. Only a slight positive trend was observed for kit 3 vs. kit 1 and kit 2 on delivery rate per thawing cycle (7.12% vs. 4.19 and 4.51%, respectively; P < 0.058) and live birth rate (3.07% vs. 2.59 and 1.93%, respectively, P < 0.069). Thawing solutions of kit 3 were similar to those of any warming protocol. CONCLUSIONS: A defined concentration of extracellular cryoprotectants in thawing/warming solutions had a beneficial effect on the embryo cryosurvival rate. Results could provide the rationale for the adoption of a single standardized warming protocol.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

Reference intervals for hemoglobin and hematocrit in a low-risk pregnancy cohort: implications of racial differences.

Objective: As anemia in pregnancy is associated with adverse perinatal outcomes, we sought to define the mean and the fifth percentile of Hb and Ht using a contemporary multiethnic large cohort of low-risk pregnancies, and assess potential racial differences. Methods: We conducted a retrospective cohort study on women who delivered between 1 January 2008 and 31 December 2013 in Reggio Emilia County, Italy. Linear mixed effects models were used to describe changes in mean Hb and Ht, while quantile regression with matrix-design bootstrap defined changes in the fifth percentile of Hb and Ht, controlling for race, maternal age, smoking, and pregnancy number. Results: We analyzed 23,657 hemograms from 7318 pregnancies and 6870 women. Multivariate analysis showed that when compared to Caucasians', African women's mean Hb and Ht were respectively 0.24 (95%CI 0.3-0.17) g/dl and 0.7 (95%CI 0.8-0.5) % lower, while Asian mothers' were 0.11 (95%CI 0.19-0.03) g/dl and 0.3 (95%CI 0.5-0.1) % inferior. Similarly, both African and Asian women had lower fifth Ht percentiles (-1, 95%CI -1.3 to -0.6, and -0.4, 95%CI -0.7 to -0.04) than Caucasians, while African mothers also had lower fifth Hb percentile (0.3, 95%CI 0.5-0.1). The fifth percentile for Hb and Ht were, respectively, 11.3 (95%CI 11-11.5) g/dl and 32.8 (95%CI 32.3-33.4) % in the first trimester, 10.4 (95%CI 10.1-10.6) g/dl and 30.2 (95%CI 29.6-30.8) % in the second trimester, 10.1 (95%CI 9.8-10.3) g/dl and 30.6 (95%CI 30-31.1) % in the third trimester. Conclusions: We provided contemporary references to define anemia in pregnancy, and we confirmed that even in pregnancy, African and Asian women have lower Hb and Ht than Caucasian. Racial and population-specific references may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment.

Pregnancy complications in infertile patients with polycystic ovary syndrome: updated evidence.

Polycystic ovary syndrome (PCOS) is a common female disorder with a pathogenesis still today not completely known. To the present, PCOS is considered more than just a reproductive disorder since several metabolic consequences that could affect women's health during different stages of reproductive and post-reproductive life were reported. The aim of the current review was to evaluate present evidence-based data regarding the pregnancy complications in infertile patients with PCOS. An extensive literature search until February 2018 was performed in PubMed, Medline, the Cochrane Library and Web of Science. Outcomes were classified in: early pregnancy complications, late pregnancy complications, perinatal complications, offspring health and long-term offspring and maternal health. Even if the exact mechanisms involved are still unclear, women with PCOS have an increased risk of pregnancy-related complications, such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia (PE), premature delivery and caesarean section. Moreover, the offspring of women with PCOS are also at increased risk of congenital anomalies and hospitalization in childhood. Further studies are needed to study the mechanism underlying pregnancy complications in PCOS and to identify any interventions to reduce the risk of obstetric and neonatal risks in women affected by PCOS and in their offspring.

"The More the Better" Paradox of Antenatal Ultrasound Examinations in Low-Risk Pregnancy.

Objective To investigate whether different antenatal care models could account for differences in operative delivery rates and adverse neonatal outcomes among low-risk pregnant women, and to identify independent variables associated with delivery modes and adverse neonatal outcomes. Study design Retrospective cohort from a single center of singleton, term, live births between January 2012 and June 2014. Rates of cesarean deliveries, operative vaginal deliveries, and neonatal morbidities were analyzed among women followed by private obstetrician-gynecologists versus national health system providers (certified nurse midwifes supervised by obstetrician-gynecologists), and adjusted for potential confounders. Results Among the 2,831 women in our cohort, obstetric and neonatal outcomes were independent of obstetric providers. After we controlled for confounders, private patients having more than four antenatal ultrasound examinations were more likely to undergo cesarean delivery than public patients with four or fewer sonographic assessments (five to eight prenatal scans: relative risk ratio, 3.3; 95% confidence interval [CI] 1.4-8; nine or more prenatal scans: relative risk ratio, 4.1; 95% CI 1.2-14). Conclusions Multiple prenatal ultrasound examinations in low-risk obstetric populations appear to be an independent and potentially modifiable risk factor for cesarean deliveries.

Intracytoplasmic morphologically selected sperm injection versus conventional intracytoplasmic sperm injection: a randomized controlled trial.

BACKGROUND: Intracytoplasmic morphologically selected sperm injection (IMSI) is still proposed and employed in the clinical practice to improve the reproductive outcome in infertile couples scheduled for conventional intracytoplasmic sperm injection (cICSI). The aim of the current randomized controlled trial (RCT) was to test the hypothesis that IMSI gives a better live birth delivery rate than cICSI. METHODS: Infertile couples scheduled for their first cICSI cycle for male factor were allocated using a simple randomization procedure. All available biological and clinical data were recorded and analyzed in a triple-blind fashion. RESULTS: Our final analysis involved the first 121 patients (48 and 73 subjects for IMSI and cICSI arm, respectively) because the trial was stopped prematurely on the advice of the data safety and monitoring Committee because of concerns about IMSI efficacy at the first interim analysis. No significant difference between arms was detected in rates of clinical pregnancy per embryo transferred [11/34 (32.3%) vs. 15/64 (23.4%); odds ratio (OR) 1.56, 95% (confidence interval) CI 0.62-3.93, P = 0.343] and of live birth delivery [9/48 (18.8%) vs. 11/73 (15.1%); OR 1.30, 95%CI 0.49-3.42, P = 0.594). CONCLUSION: Current data did not support the routine use of IMSI in the clinical practice for improving cICSI results in unselected infertile couples with male factor.

Complications and challenges associated with polycystic ovary syndrome: current perspectives.

Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome's risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up.

Pregnancy complications in women with polycystic ovary syndrome.

BACKGROUND: The great majority of studies performed so far concerning women diagnosed with polycystic ovary syndrome (PCOS) have focused on diagnosis, menstrual cycle abnormalities, hirsutism and infertility. Although progress has been made in developing methods for achieving a pregnancy and reducing multiple gestations in women with PCOS, little attention has been paid to pregnancy complications and subsequent child outcomes. This review aims to summarize current knowledge regarding the clinical and pathophysiological features of pregnancy and children in women with PCOS. METHODS: A literature search up to April 2015 was performed in PubMed, Medline, the Cochrane Library and Web of Science without language restriction. All articles were initially screened for title and abstract and full texts of eligible articles were subsequently selected. Systematic reviews with meta-analysis were initially included for each specific subject. Recent randomised controlled trials (RCTs), which were not included in the systematic reviews, were also included. In addition to evidence from meta-analyses or RCTs, we used non-randomized prospective, uncontrolled prospective, retrospective and experimental studies. When specific data for patients with PCOS were lacking, results from general population studies were reported. RESULTS: Women with PCOS exhibit a clinically significant increased risk of pregnancy complications compared with controls. Data which were not adjusted for BMI or other confounders demonstrated in PCOS a 3-4-fold increased risk of pregnancy-induced hypertension and pre-eclampsia, a 3-fold increased risk of gestational diabetes and 2-fold higher chance for premature delivery. Features characteristic of PCOS, such as hyperandrogenism, obesity, insulin resistance and metabolic abnormalities, may contribute to the increased risk of obstetric and neonatal complications. Limited available data suggest that offspring of women with PCOS have an increased risk for future metabolic and reproductive dysfunction. Underlying pathophysiological mechanisms of pregnancy complications along with its association with health of offspring remain uncertain. To date, the strategies for prevention and management of pregnancy complications in women with PCOS, and whether long-term health of these women is influenced, and to what extent, by pregnancy and/or pregnancy complications, remain to be elucidated. CONCLUSIONS: Women with PCOS show an increased risk of pregnancy complications. Heterogeneous aetiological factors involved in PCOS and associated co-morbidities may all be involved in compromised pregnancy and child outcomes. In women with PCOS, a possible relationship with genetic, environmental, clinical and biochemical factors involved in this complex condition, as well as with pregnancy complications and long-term health for both mother and child, remains to be established.

Safety and efficacy of the minilaparotomy for myomectomy: a systematic review and meta-analysis of randomized and non-randomized controlled trials.

Myomectomy is the most frequent reproductive surgery to preserve, improve fertility, or both. The present study was designed to assess the safety and efficacy of minilaparotomy for myomectomy through a systematic review of randomized and non-randomized controlled trials with a meta-analysis. All available studies comparing minilaparotomy myomectomy with laparotomy, other minimally invasive surgeries, or both, were included. Available surgical and reproductive data were extrapolated, and a qualitative and quantitative analysis was carried out. Fourteen studies were included in the final analysis for an overall sample of 2151 patients. A total of 1139 patients were treated with minilaparotomy, whereas 239 and 773 patients were treated, respectively, with the laparotomy or laparoscopy. Only two studies comparing minilaparotomy with laparoscopy assessed the reproductive outcomes, and their data synthesis did not demonstrate significant difference between the two surgical techniques. Specific surgical end-points differed significantly between minilaparotomy and laparotomy or laparoscopy, even if those differences were not clinically relevant. In conclusion, current data do not permit a definite conclusion to be drawn. Further studies are needed to clarify the risk-benefit ratio of the minilaparotomy compared with the other minimally invasive surgical procedures for myomectomy to provide clinical recommendations with strong scientific evidence.

Primary diffuse large B-cell lymphoma of the uterus: case report and review.

BACKGROUND: Primary diffuse large B-cell lymphoma of the cervix is a very rare disease, with non-specific clinical presentation. Its prognosis depends on accurate and timely diagnosis and therapy. Moreover, the management of this tumour has never been standardized. CASE REPORT: Herein we present a rare case of primary diffuse large B-cell lymphoma of the cervix misdiagnosed as cervical myoma. Our systematic review of the English literature identified 143 cases of primary diffuse large B-cell lymphoma of the uterus. Patients' characteristics and oncological, surgical, and safety data were recorded and analyzed. CONCLUSION: Although rare, primary diffuse large B-cell lymphoma of the cervix should never be ruled-out. Given its non-specific clinical symptoms, a multidisciplinary approach is required to perform a timely diagnosis and administer appropriate therapy. Immunochemotherapy (Rituximab + CHOP or CHOP-like regimen) with/without radiotherapy is the most common and most effective treatment; surgery should be avoided.