Pregnancy and perinatal outcomes of early vs late selective termination in dichorionic twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To evaluate outcomes of dichorionic twin pregnancies undergoing early vs late selective termination of pregnancy (ST). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to March 2022. The primary outcome of this study was pregnancy loss prior to 24 weeks' gestation. The secondary outcomes included preterm birth (PTB) before 37, 34, and 32 weeks, preterm prelabor rupture of membranes (PPROM), gestational age (GA) at delivery, Cesarean delivery, mean birth weight, 5-min Apgar score < 7, overall neonatal morbidity and neonatal survival. Only prospective or retrospective studies reporting data on the outcome of early (before 18 weeks) vs late (at or after 18 weeks) ST in dichorionic twin pregnancies were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale for cohort studies. Random-effects head-to-head meta-analysis was used to analyze the data. RESULTS: Seven studies reporting on 649 dichorionic twin pregnancies were included in this systematic review. The risk of pregnancy loss prior to 24 weeks was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST (1% vs 8%; odds ratio (OR), 0.25 (95% CI, 0.10-0.65); P = 0.004). The risk of PTB was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST when considering PTB before 37 weeks (19% vs 45%; OR, 0.36 (95% CI, 0.23-0.57); P < 0.00001), before 34 weeks (4% vs 19%; OR, 0.24 (95% CI, 0.11-0.54); P = 0.0005) and before 32 weeks (4% vs 20%; OR, 0.21 (95% CI, 0.05-0.85); P = 0.03). The mean birth weight was significantly greater in the early-ST group (mean difference (MD), 392.2 g (95% CI, 59.1-726.7 g); P = 0.02), as was the mean GA at delivery (MD, 2.47 weeks (95% CI, 0.04-4.91 weeks); P = 0.049). There was no significant difference between dichorionic twin pregnancies undergoing early compared with late ST in terms of PPROM (P = 0.27), Cesarean delivery (P = 0.38), 5-min Apgar score < 7 (P = 0.35) and neonatal survival of the non-reduced twin (P = 0.54). CONCLUSIONS: The risk of pregnancy loss prior to 24 weeks and the rate of PTB before 37, 34 and 32 weeks were significantly higher in dichorionic twin pregnancies undergoing late vs early ST, thus highlighting the importance of early diagnosis of fetal anomalies in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.

Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Macroscopic and microscopic findings of the placenta in women with polycystic ovary syndrome.

STUDY QUESTION: Do patients with polycystic ovary syndrome (PCOS) have macroscopic and/or microscopic placental alterations? SUMMARY ANSWER: The placental structure in patients with PCOS, even in those with uncomplicated pregnancy, is altered. WHAT IS KNOWN ALREADY: The spectrum of pregnancy complications seems to have a common denominator: a defective trophoblast invasion and placentation. In women with PCOS, alterations in endovascular trophoblast invasion related to insulin resistance and hyperandrogenism have been observed. STUDY DESIGN, SIZE, DURATION: For this prospective case-control study, 30 pregnant patients with PCOS (cases) and 60 healthy pregnant women without PCOS features (controls) were enrolled and studied until delivery. Clinical, biochemical, ultrasonographic and obstetric data were recorded. The baseline clinical and biochemical data for screening for PCOS and for inclusion/exclusion were obtained before the seventh week of gestation. At delivery, placentas were collected and detailed macroscopic and microscopic analyses were performed. PARTICIPANTS, SETTING, METHODS: Cases and controls were matched for age and BMI (all <30 kg/m(2)). The matching procedure was one-to-two. Only subjects with spontaneous conception and uncomplicated pregnancies were included in the final analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Placental weight (P = 0.04), thickness (P = 0.02), density (P = 0.02) and volume (P = 0.01) were significantly inferior in women with, compared with those without PCOS. The placentas from patients with PCOS more frequently had an irregular shape (P = 0.03) and a higher cord coiling index (P = 0.02). Differences between cases and controls also concerned the extent of villous (P = 0.04) and intervillous (P = 0.01) spaces, the extent of fibrosis (P = 0.03), endovascular trophoblast (depth, extension and morphometry) (P < 0.05) and mitotic activity (P = 0.01). The percentage of patients with lesions [22/30 (73.3%) versus 25/60 (41.7%), respectively; P = 0.01] and the mean number of placental lesions (3.5 ± 2.1 versus 1.4 ± 1.1, respectively; P = 0.02) were higher in the PCOS than the control group. The odds ratio for placental alterations, adjusted for weight gain, was 2.8 (95% confidence interval 1.3-9.9). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was the selection of a specific PCOS sample, which is probably not representative of the PCOS phenotype as a whole. In fact, we excluded patients with PCOS who were obese and who achieved a pregnancy following the use of ovulation inductors or assisted reproduction techniques. WIDER IMPLICATIONS OF THE FINDINGS: The present study is the first to demonstrate that the morphology and microscopic structure of placenta in patients with PCOS with an uncomplicated pregnancy are altered. Further studies are needed to assess a correlation of these changes with the increased risk of obstetric complications observed in some pregnancies of women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflict of interest and no financial support for the research. TRIAL REGISTRATION NUMBER: N/A.

[Assessment of the modification of the clinical, endocrinal and metabolical profile of patients with PCOS syndrome treated with myo-inositol]. / Valutazione delle modificazioni del profilo clinico, endocrino e metabolico di pazienti con sindrome dell'ovaio policistico in trattamento con mio-inositolo.

AIM: Aim of the study was to evaluate the effects of 24 weeks administration of myo-inositol plus folic acid (Inofert ®) on clinical, endocrine and metabolic parameters of polycystic ovary syndrome (PCOS) patients. METHODS: Seventy women, 18 to 35 years, were enrolled; 35 patients were enrolled as study group and treated with Inofert ® (200 µg folic acid plus myo-inositol 2 g per day) for 24 weeks. The other 35 patients, similar at baseline to patients in the study group, were enrolled as control group and received no treatment. In all patients the restoration of ovulation and variations of the endocrine and metabolic profile after treatment were assessed. RESULTS: After 24 weeks, only five of 35 patients treated with Inofert® and 14 of 35 patients in the control group remained anovulatory and this difference was statistically significant. Body mass index decreased significantly in the study group, while a non-significant increasing was recorded in the control group. Moreover, non-significant reduction in circulating levels of LDL, and a statistically significant increase in the levels of HDL in the study group were observed. CONCLUSION: Treatment with Inofert® allows to restore rapidly spontaneous ovulation in amenorrheic patients with PCOS and shows a significant advantage in terms of reduction in BMI and a positive trend in terms of changes in serum lipid profile.

'Guess who'? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations.

OBJECTIVES: Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. STUDY DESIGN: Multicentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease' localizations. RESULTS: Having green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42-9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13-0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02-14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13-16.09; p < 0.001). CONCLUSIONS: The association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.

Effects of highly purified follicle-stimulating hormone on sperm DNA damage in men with male idiopathic subfertility: a pilot study.

BACKGROUND: Gonadotropins administration have been demonstrated effective for the treatment of idiopathic male infertility, even if no clear data regarding their specific mechanism of action on semen quality are at the moment available. AIM: To evaluate the effect of highly purified FSH (hpFSH) administration on standard semen parameters, sperm oxidative stress, and sperm chromatin structure and DNA fragmentation. MATERIAL AND METHODS: In the current prospective baseline-controlled study, 36 subjects with male idiophatic infertility were enrolled. Baseline clinical and biochemical data were evaluated. Before and after 3 months of treatment with hpFSH, sperm samples were collected and standard semen analysis, reactive oxygen species (ROS) assessment and sperm DNA fragmentation were evaluated. RESULTS: A significant (p<0.05) improvement from baseline in standard seminal parameters was observed. A significant (p<0.05) reduction in sperm ROS levels and DNA fragmentation was observed. Statistically significant (p<0.05) correlations between variation in ROS levels and both seminal parameters and DNA fragmentation variations were detected. CONCLUSIONS: Three months of hpFSH administration seems to reduce ROS and DNA damage in subjects with male idiopathic subfertility improving semen parameters. Further evidences from well-designed randomized double-blind placebo- controlled studies are needed in order to confirm our preliminary results.

[A retrospective analysis comparing colposuspension and retropubic mid-urethral sling as preventive anti-incontinence measures during laparoscopic sacrocolpopexy]. / Analisi retrospettiva di confronto tra colposospensione e sling retropubica medio-uretrale come misure preventive anti-incontinenza in corso di sacrocolpopessia laparoscopica.

AIM: The aim of this paper was to compare two anti-incontinence procedures during laparoscopic sacrocolpopexy (LSC) to prevent postoperative stress urinary incontinence (SUI). METHODS: Retrospective analysis of 90 continent hysterectomized patients with vaginal vault prolapse treated with LSC plus colposuspension (group A, N.=30), LSC plus retropubic mid-urethral sling (group B, N.=30), or LSC alone (group C, N.=30). RESULTS: De novo SUI rate resulted significantly (P<0.05) lower in group B than C. No difference was detected regarding de novo urge urinary incontinence. Total reoperation rate resulted significantly (P<0.05) higher in group A than B and lower in group B than C. CONCLUSION: When associated to LSC for preventing SUI, colposuspension and retropubic mid-urethral sling are effective and safe, even if mid-urethral sling seems to provide the best risk/benefit profile.

[Sex ratio in the offspring of pregnant women with polycystic ovary syndrome: effect of different phenotypes]. / Sex ratio nella prole di donne affette dalla sindrome dell'ovaio policistico: effetti dei differenti fenotipi.

AIM: The aim of this paper was to investigate the sex ratio in the offspring of pregnant patients with polycystic ovary syndrome (PCOS). METHODS: Analysis of 70 pregnant patients with PCOS who achieve a pregnancy without any kind of treatment, and having as controls 63 healthy pregnant women without any feature of PCOS. RESULTS: No significant difference in sex ratio was detected between PCOS and controls, even if it resulted significantly different in the full-blown and non-PCO phenotypes. CONCLUSION: The PCOS phenotypes influenced the sex ratio in the offspring, suggesting that environmental factors could play a role in determination of the offspring gender.

A New Combined Laparoscopic-Vaginal Lateral Suspension Procedure for the Treatment of Pelvic Organ Prolapse.

OBJECTIVE: To show an original technique of a new combined vaginal-laparoscopic lateral suspension in Hysteropexy with cistocele and rectocele. In recent years, changes in attitudes toward sexuality, psychological value of reproductive organs and the desire to preserve fertility have led to a growing interest in uterine-preserving surgery for Pelvic Organ prolapse. Minimally invasive procedures derived from sacrocolpopexy are considered the gold standard in the treatment of apical Pelvic Organ prolapse. However, dissection at the level of the promontory may be challenging, particularly in obese women and when an anatomical variation exists. This may be associated with rare but serious neurological or ureteral morbidity as well as life-threatening vascular injury. MATERIALS AND METHODS: Stepwise demonstration of the technique with narrated video footage. Local institutional review board was consulted, and this study was exempted from approval. RESULTS: Our technique entails 2 times. During the vaginal time, a polypropylene mesh is fixed to the cervical fascia and the 2 extremities are introduced in the abdominal cavity through the Douglas pouch. During the laparoscopic time, a retroperitoneal tunnel is made along the walls of the lateral abdominal walls; thereafter, each of the 2 extremities of the mesh is passed through the omolateral tunnel and "tension-free" suspended to the abdominal wall. CONCLUSION: Our combined technique may allow a safer approach, reducing the risks of serious complications. Moreover, it leads to a more physiological orientation of the vaginal axis. Further controlled studies are needed to confirm our suggestion.

Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. METHODS: A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. RESULTS: After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. CONCLUSIONS: In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.

Uterine blood flow in pregnant patients with polycystic ovary syndrome: relationships with clinical outcomes.

OBJECTIVE: To study the impedance to blood flow through the uterine artery in pregnant women with polycystic ovary syndrome (PCOS), and to evaluate its predictive value for adverse pregnancy and perinatal outcomes in this population. DESIGN: Prospective case-control study. SETTING: Academic Departments of Obstetrics and Gynaecology in Italy. POPULATION: Seventy-three pregnant women with ovulatory PCOS (PCOS group) and 73 age- and body mass index-matched healthy pregnant controls (control group). METHODS: Serial Doppler velocimetry measurements of the uterine artery. MAIN OUTCOME MEASURES: Blood flow impedance indices and pregnancy/perinatal outcomes. RESULTS: A significantly (P < 0.05) higher rate of subjects with abnormal velocimetry findings was observed in the PCOS group than in the control group. In the PCOS group, the pulsatility index (PI) at first (P = 0.042) and mid-second (P = 0.039) trimesters of pregnancy, and bilateral notch at first (P = 0.025) and mid-second (P = 0.007) trimesters of pregnancy, were the strongest independent predictors of adverse outcomes. Conversely, in the control group, PI at the first trimester of pregnancy was a predictor of adverse outcomes only when combined with bilateral notch (P = 0.042), whereas at mid-second trimester of pregnancy PI (P = 0.033) and bilateral notch (P = 0.048) were independent predictors of adverse outcomes. CONCLUSIONS: Uterine artery Doppler indices are more commonly altered in pregnant patients with PCOS than in controls, showing a high predictive value for abnormal pregnancy/perinatal outcomes.

Relugolix for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions. AREAS COVERED: The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. It is an orally active non-peptide Gonadotropin-releasing hormone (GnRH)-receptor antagonist recently licensed for women with symptomatic fibroids. Relugolix is a well-tolerated safe drug; it is effective in inducing a dose-dependent decrease in menstrual blood loss, with faster reduction of heavy menstrual bleeding (HMB) and a greater shrinkage in fibroid volume compared to the current standard of GnRH agonist treatment. EXPERT OPINION: Relugolix is a promising drug for the non-surgical treatment of women with UF. To date, the only published data come from a well-selected Japanese female population study while results from worldwide ongoing studies are ongoing in order to confirm the efficacy of this GnRH agonist receptor.

Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study.

BACKGROUND: Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. METHODS: Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. RESULTS: The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P < 0.05) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P < 0.05) from baseline and were significantly different (P < 0.05) between the two groups. CONCLUSIONS: Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.