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Placentation and complications of ART pregnancy. An update on the different possible etiopathogenic mechanisms involved in the development of obstetric complications.

INTRODUCTION: Infertile couples' percentage is increasing all over the world, especially in Italy, with high number of children born in our country through assisted reproductive techniques (ART). However, pregnancies obtained by ART have increased potential obstetrical risks which could be caused by fetus-placenta unit development, most of all due to placentation's evolution. These can be reassumed into miscarriage, chromosomal abnormalities, preterm delivery, multiple pregnancy, IUGR, placenta previa, abruptio placentae, preeclampsia and hypertensive disorders, postpartum hemorrhage. METHODS: The aim of this article is to evaluate hypothetic mechanism involved in placentation process and in the etiopathology of ART pregnancies disorders, giving an updating overview of different etiopathogenetic pathways and features. On this scenario, we create an updated review about the etiopathogenesis of abnormal placentation in ART pregnancies. RESULTS: Several features and different etiopathogenetic characteristic might impact differently such as advanced maternal age, poor ovarian reserve, oocyte quality and causes of subfertility themselves, and the ART techniques itself, as hormonal medical treatments and laboratory techniques such as gamete and embryo laboratory culture, cryopreservation versus fresh ET, number of embryos transferred. CONCLUSION: To further explore the molecular mechanisms behind placentation in ART pregnancies, further studies are necessary to gain a better understanding of the various aspects involved, particularly those which are not fully comprehended. This could prove beneficial to clinicians in both ART care and obstetric care, as it could help to stratify obstetrical risk and decrease complications in women undergoing ART, as well as perinatal disorders in their children. Correct placentation is essential for a successful pregnancy for both mother and baby.

The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD (p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days (p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients (p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved.

Sexual function analysis and clitoral vascularization in postmenopausal women with genitourinary syndrome treated with ospemifene.

BACKGROUND: The aim of this study was to evaluate the efficacy of ospemifene in the Vaginal Health Index (VHI), in the vulvovaginal vascular perfusion, and to assess its impact on quality of life and sexual function. METHODS: Among 52 eligible patients, 43 consecutive postmenopausal patients affected by vulvo-vaginal atrophy (VVA), or genitourinary syndrome (GSM) were evaluated. VVA evaluation and ultrasound of the vulvo-vaginal vascularization by sampling the Pulsatility Index (PI) of clitoris dorsal artery were performed before and after 3 months-treatment with ospemifene. The 36-Item Short Form Survey (SF-36) for the quality-of-life assessment before and after 3 months were available for all women; instead, Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires for the sexual function evaluation were performed for sexually active women in the study. The Patient Impression of Global Improvement (PGI-I) after 3 months of treatment was also calculated. RESULTS: The number of sexually active women significantly increased after 3 months (26 [60.46%] vs. 35 [81.39%]; P=0.01). The mean number of intercourses during the treatment increased (12.87±3.43 vs. 15.79±3.12, P=0.03). The PI of clitoris dorsal artery has significantly changed before and after treatment respectively (PI [1.69±0.42 vs. 1.28±0.45, P=0.001] RI [0.74±0.11 vs. 0.54±0.15, P=0.001]). The FSFI, FSDS and SF-36 Questionnaires scores showed a significant improvement after 3 months. VHI and PI were the independent factors of a lower FSFI after 3 months of treatment at multivariate analysis. CONCLUSIONS: Ospemifene improve the VHI and vulvovaginal vascular perfusion demonstrating a positive impact on sexual function and quality of life.

Systemic vascular resistance may influence the outcome of in vitro fertilization.

Introduction: The number of pregnancies obtained through in vitro fertilization (IVF) techniques are increasing, and only few studies have investigated hemodynamic variations in women undergoing IVF techniques. The aim of this study was to evaluate the hemodynamic parameters in women undergoing IVF, to assess a possible correlation between hemodynamics and embryo implantation.Methods: 45 normotensive non-obese women, age ≤ 43 years, with idiopathic or tubal infertility, referred to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2020/2021, underwent IVF techniques. All women were evaluated with Ultra Sonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters at two different stages: at the mid-luteal phase, before the beginning of IVF, and at the day of embryo transfer (dET). All demographics and hormonal parameters in both groups were comparable. The hemodynamic parameters were compared between women with a positive ß-HCG test vs. those testing negative.Results: 11 out of 45 (24,5%) women obtained positive ß-HCG test. All demographics and hormonal parameters were comparable in both groups. Women with a positive ß-HCG test showed statistically lower systemic vascular resistance (SVR) at mid-luteal phase (868.61 ± 100.1 vs. 1009 ± 168.4) and dET (818,9 ± 104.5 vs 1038.52 ± 150.82 dynes × s/cm5).Conclusions: Hemodynamic assessment can identify a more favorable pre-pregnancy cardiovascular adaptation. Embryo implantation might be positively influenced by the hemodynamic parameters, e.g. lower SVR, before the beginning of IVF techniques, and during the window of implantation.

Laparoscopic stripping versus endometrioma ethanol sclerotherapy in women with endometrioma awaiting IVF: a long-term analysis of ovarian reserve and pregnancy outcome.

BACKGROUND: The aim of this study was to compare ovarian reserve, oocytes quality and pregnancy outcome of endometrioma treatment by laparoscopic stripping (LS) versus endometrioma ethanol sclerotherapy (EST) in infertile women awaiting in-vitro fertilization (IVF). METHODS: Retrospective analysis was performed. Twenty-three women underwent EST and 26 women LS. Intra- and postoperative complications were recorded. The women were followed-up for 36 months for cyst recurrence, oocytes quality and pregnancy outcome. Serum anti-Müllerian hormone (AMH) levels after treatment were measured to observe the impact on the ovarian reserve. Women's satisfaction was investigated with PGI-I. RESULTS: During follow-up, there were 3 endometriomas recurrences after LS and none after EST. Six months after treatment AMH was 3.17±2.15 in EST vs. 2.22±1.97 in LS, P=0.045. Symptoms' improvement was comparable. No intraoperative complications occurred. In the LS group the postoperative complications were significantly higher. After IVF cycles, the quality of the retrieved oocytes was the same. In EST group, clinical pregnancy (48.1% vs. 19.6%) and live birth rates (36.5% vs. 14.3%) were significantly increased compared to LS. Women's satisfaction was comparable at PGI-I. Both EST and the presence of an endometrioma sized 6 cm or less proved to be independent factors of a better live birth rate in multivariate analysis. CONCLUSIONS: EST efficacy was greater than LS for endometrioma. Ovarian function was well preserved. Hospital stay was shorter, fewer complications occurred. Pregnancy outcome was better after EST.

Management of women with uterine fibroids in reproductive center: retrospective analysis of clinical and reproductive outcomes.

BACKGROUND: Uterine fibroids are the most common benign tumor in women. According to literature, submucosal myomas have a negative effect on reproductive outcomes in women undergoing assisted reproductive techniques (ART) but there are fewer data concerning intramural fibroids. During last years, ulipristal acetate (UPA) 5 mg was widely used as medical option of fibroid's treatment, but from 2020, the Pharmacovigilance Risk Assessment Committee (PRAC) has revoked the marketing authorization after some cases of liver toxicity. METHODS: In this observational, retrospective study we collected data from a sample of 23 women affected by symptomatic uterine fibroids (from type 1 to type 7 according FIGO classification) followed in our center for assisted reproduction from 2016-2019. All patients received 5 mg/day UPA for three months, followed by two months of wash-out therapy. A group of 13 women treated with UPA, with intramural fibroid not distorting the uterine cavity, after wash-out therapy, affected by tubal or idiopathic factors of infertility too, underwent ART. We also evaluated a control group of women, not affected by fibroids, randomly selected from a general group of our ART patients, similar by age, BMI, and cause of infertility only idiopathic or tubal factors. We evaluated the impact of UPA on reduction of fibroid volume, symptomatology and distortion of the cavity in all the women treated, and the IVF (in-vitro fertilization) outcome between the fibroid group of women affected by intramural fibroids who underwent ART, and the control group. RESULTS: In all the women treated with UPA the overall median fibroid volume pretreatment was 45.168±35.360 mm3, that decreased to a mean value of 22.592±22.116 mm3 post one cycle of UPA, with an overall mean decrease of -22.586 mm3 (of 49%) statistically significant (P=0.00001). After treatment, the distortion of the uterine cavity reduced in high percentage of cases: 85,71% (type 1-2), χ2 difference in respect to the value pretreatment of 0.3941, and 86.96% of patients subjectively referred an improvement in the symptomatology. In the group of 13 women that undergone ART, after one IVF cycle for each patient, we obtained 61% of positivity of dosage of beta human chorionic gonadotropin (hCG) after UPA treatment, and we obtained a similar value in the control group. CONCLUSIONS: In our little sample we have observed that UPA represented a valid non-invasive medical treatment strategy for fibroids in women candidate for (IVF, not only in women affected by sub-mucosal, but also by intramural fibroids not distorting uterine cavity. After a single, three months course of treatment, we obtained good results in terms of reduction of fibroid's volume and improvement of symptomatology, without side effects, preparing a more favorable environment for ART.

Mature Ovarian Teratoma: Neurological Implications in a Young Woman.

Anti-NMDAR encephalitis is an autoimmune syndrome associated with antibodies against NMDA receptors. In some cases, it is associated with various tumors; one of them is ovarian teratoma, which mostly affects women below the age of 30 years. Here, we report a case of ovarian teratoma associated with anti-NMDAR encephalitis treated with both laparoscopic surgery and immunotherapy. Multidisciplinary approach is the cornerstone for the management of this syndrome.

Positive Impact of Levothyroxine Treatment on Pregnancy Outcome in Euthyroid Women with Thyroid Autoimmunity Affected by Recurrent Miscarriage.

Impaired thyroid hormone availability during early pregnancy is associated with recurrent miscarriage (RM) and adverse pregnancy outcomes. The main cause of thyroid dysfunction is thyroid-related autoimmunity (TAI), characterized by a significantly higher serum level of thyroid-stimulating hormone (TSH) compared to that of women without thyroid autoimmunity. TAI is associated with a significantly increased risk of miscarriage, and the incidence of TAI in women experiencing RM is higher compared to normal fertile women. In the present study, we have performed a retrospective analysis comparing the ability to conceive, the number of miscarriages and full-term pregnancies between 227 euthyroid women with autoimmune thyroid disease affected by RM and treated with levothyroxine (LT4) as adjuvant therapy, and a control group of 230 untreated women. We have observed a significant improvement of full-term pregnancies in treated women (59%) compared to untreated women (13%, p < 0.0001). Compared to the control group, treated women had a lower percentage of miscarriages (12% vs. 30%) and improved capacity to conceive (57% vs. 29%). Using age as a variable, the outcome in women younger than 35 years was not influenced by the LT4 therapy. Whereas, in women over 35 years, supplementation with LT4 significantly reduced the miscarriage rate (p < 0.05). We can conclude that a transient impairment of TH availability, not easily detectable before pregnancy, could be an important cause of RM in a subset of euthyroid women with autoimmune thyroid disease. This transient impairment may be reverted using adjuvant treatment with low doses of LT4.