Transition from pediatrics to adult health care in girls with turner syndrome.

INTRODUCTION: Turner Syndrome is a rare condition secondary to a complete or partial loss of one X chromosome, leading to a wide spectrum of clinical manifestations. Short stature, gonadal dysgenesis, cardiovascular malformations, and dysmorphic features characterize its common clinical picture. AREAS COVERED: The main endocrine challenges in adolescent girls with Turner Syndrome are puberty induction (closely intertwined with growth) and fertility preservation. We discuss the most important clinical aspects that should be faced when planning an appropriate and seamless transition for girls with Turner Syndrome. EXPERT OPINION: Adolescence is a complex time for girls and boys: the passage to young adulthood is characterized by changes in the social, emotional, and educational environment. Adolescence is the ideal time to encourage the development of independent self-care behaviors and to make the growing girl aware of her health, thus promoting healthy lifestyle behaviors. During adulthood, diet and exercise are of utmost importance to manage some of the common complications that can emerge with aging. All clinicians involved in the multidisciplinary team must consider that transition is more than hormone replacement therapy: transition in a modern Healthcare Provider is a proactive process, shared between pediatric and adult endocrinologists.

Fertility preservation in pregnant cancer patients after first-trimester abortion: a new challenge with possible solutions.

Fertility preservation in pregnant women recently diagnosed with cancer can be a challenge. Raised levels of human chorionic gonadotropin (Beta-hCG) and progesterone in this population of patients may pose a problem for the prompt initiation of controlled ovarian stimulation (COS) due to a potential negative feedback of these hormones on folliculogenesis; however, it is not feasible to wait for negativization of serum beta-hCG levels before starting controlled ovarian stimulation. In literature, very few cases have been reported regarding the preservation of fertility in pregnant women recently diagnosed with cancer. We performed an extended revision of the literature to evaluate the current knowledge of the management of fertility preservation in women with cancer and we examined two cases closely. The first case study involved a cancer patient who underwent surgical abortion at 6.5 weeks of gestation followed by administration of mifepristone to detach any minimal residual trophoblast and consequently to decrease serum beta-hCG and progesterone levels before starting COS. In the second case study, the cancer patient underwent surgical abortion at 7.1 weeks of gestation and simultaneous unilateral oophorectomy for ovarian tissue cryopreservation due to a limited time for COS. By analyzing the results of these studies, it could be hypothesized that mifepristone administration may favor the decrease of serum beta-hCG and progesterone levels in order to permit rapid initiation of COS. In cases where COS is not feasible, ovarian tissue cryopreservation should be considered as an alternative fertility preservation technique.

Intrahepatic cholestasis of pregnancy after ovarian hyperstimulation syndrome with wild-type ABCB4 gene: a peculiar case and literature review.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) in the first trimester occurring after ovarian hyperstimulation syndrome (OHSS) is a rare condition and few cases are reported in the literature. Hyperestrogenism may explain this problem in genetically predisposed women. The objective of this article is to report one of these rare cases and offer an overview of the other published cases. CASE PRESENTATION: We report a case of severe OHSS followed by ICP in the first trimester. The patient was admitted to the intensive care unit and was treated according to the guidelines for the management of OHSS. Moreover, the patient also received ursodeoxycholic acid for ICP, which brought to an improvement of her clinical conditions. The pregnancy continued without other complications until the 36th week of gestation, when the patient developed ICP in the third trimester and underwent cesarean section for increased bile acid levels and cardiotocographic (CTG) pathologic alterations. The newborn was a healthy baby weighing 2500 gr. We also reviewed other case reports published by other authors about this clinical condition. We present what is, to our knowledge, the first case of ICP developed in the first trimester of pregnancy after OHSS in which genetic polymorphisms of ABCB4 (MDR3) have been investigated. CONCLUSIONS: ICP in the first trimester might be induced by elevated serum estrogen levels after OHSS in genetically predisposed women. In these women, it might be useful to check for genetic polymorphisms to know if they have a predisposition for ICP recurrence in the third trimester of pregnancy.

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3-0.4; I2 = 99%), decreasing to 1% (95% CI 0.00-0.01; I2 = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25-2.34; I2 = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

Membranous dysmenorrhoea in a woman undergoing hormone replacement preparation for embryo transfer - a peculiar case.

Membranous dysmenorrhoea is an uncommon condition characterized by the spontaneous flaking of endometrium into a single piece that maintains the shape of the uterus. The common symptom of membranous dysmenorrhoea is a colicky pain caused by uterine contractions. Because only a limited number of cases have been published in the literature, the case report we present is peculiar. This report describes a case of membranous dysmenorrhoea that occurred after an artificial frozen thawed embryo transfer cycle using vaginal progesterone. The patient, during hormone replacement treatment, reported an intense abdominal colicky pain resulting in the loss of membranous endometrial tissue. A histopathological exam was performed with a clear diagnosis of membranous dysmenorrhoea. Moreover, photos were recorded and provided together with this article. The importance of such a case report relies on the actual debate about the appropriate progesterone route of administration. Although different medical approaches exist, progesterone administration is the most widespread. However, the intramuscular, oral, and subcutaneous means of administration are gaining popularity. On this peculiar case report, the patient underwent a subsequent frozen thawed embryo transfer cycle with subcutaneous progesterone administration. The embryo transfer resulted first in a clinical pregnancy and subsequently in a spontaneous delivery without any complications.

Long-Lasting Effects of Spironolactone after its Withdrawal in Patients with Hyperandrogenic Skin Disorders.

OBJECTIVE: Hyperandrogenic skin disorders, such as hirsutism, acne and alopecia, affect approximately 10-20% of women of reproductive age, reducing quality of life and causing psychological impairment. Spironolactone is a commonly used antiandrogen, especially in women who are not sexually active or have contraindications to hormonal contraceptives. The aim of this study was to evaluate the effects of spironolactone, especially after its withdrawal, in patients with hyperandrogenic skin disorders. METHODS: Retrospective analysis of 63 women with hyperandrogenic skin symptoms due to polycystic ovary syndrome (PCOS), treated with spironolactone for at least 6 months as first-line treatment. RESULTS: After a mean time of treatment of 25.7 months, all patients reported a significant improvement in hyperandrogenic skin disorders; only 5 patients were dissatisfied and required the addition of an oral contraceptive. The therapy was well tolerated and the most frequent side-effect was intermestrual bleeding in 68.2% of cases, affecting mainly classic PCOS phenotype. Thirthyeight patients showed prolonged effects 33.7 months after spironolactone withdrawal, whereas 20 relapsed 17.5 months after discontinuation. No significant difference in clinical and biochemical parameters was observed between these two groups both at baseline and after spironolactone treatment. Ovulatory PCOS patients were treated for a shorter time and reported earlier relapse than classic PCOS patients. CONCLUSION: Spironolactone is an effective and safe treatment for hyperandrogenic skin disorders, showing long-lasting effects even several months after its discontinuation.

Telemedicine for Virtual Consultations During COVID-19 Pandemic in a Medically Assisted Reproduction Center: Patients' Perspective.

Background: Restrictive measures imposed to prevent COVID-19 contagion have caused an increase in waiting times for other health procedures. During the pandemic, utilization of telemedicine has increased to ensure patient care safely. The aim of this study was to evaluate the perspective of infertile patients who underwent virtual consultations for infertility. Materials and Methods: This was an observational study. A survey was submitted to patients who attended a virtual consultation at a single in vitro fertilization (IVF) unit between March 2020 and July 2021. The survey concerned their experience with telemedicine assessing the experience of video consulting and the software characteristics. Results: The survey response rate was 50.3% (n = 159). In total, 98.8% of patients positively rated the experience of telemedicine. Regarding the software itself, it was defined as intuitive and easy to use by 87.4% of patients. A majority (92.5%) of interviewed patients reported that they were able to receive the information and clear any doubts they had and 85.5% of interviewed patients would repeat the experience of video consultation. Conclusions: The acceptance of telemedicine was very high among infertile patients. However, IVF treatments have a strong emotional component and face-to-face consultation with medical staff might help to create the right climate of trust, and the empathy that can be demonstrated during a vis-à-vis meeting cannot be achieved through a screen. The use of telemedicine should be considered in those situations where it is not possible to attend an in-person consultation or when couples prefer it.

Uterine Septum with or without Hysteroscopic Metroplasty: Impact on Fertility and Obstetrical Outcomes-A Systematic Review and Meta-Analysis of Observational Research.

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using electronic bibliographic databases (Medline, Scopus, Embase, Science direct). Study eligibility criteria: we included in this meta-analysis all types of observational studies that evaluated the clinical impact of the uterine septum and its resection (hysteroscopic metroplasty) on reproductive and obstetrics outcomes. The population included were patients with a diagnosis of infertility or recurrent pregnancy loss. Study appraisal and synthesis methods: outcomes were evaluated according to three subgroups: (i) Women with untreated uterine septum versus women without septum (controls); (ii) Women with treated uterine septum versus women with untreated septum (controls); (iii) Women before and after septum removal. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the outcome measures. A p-value < 0.05 was considered statistically significant. Subgroup analysis was performed according to the depth of the septum. Sources of heterogeneity were explored by meta-regression analysis according to specific features: assisted reproductive technology/spontaneous conception, study design and quality of papers included Results: data from 38 studies were extracted. (i) septum versus no septum: a lower PR and LBR were associated with septate uterus vs. controls (OR 0.45, 95% CI 0.27−0.76; p < 0.0001; and OR 0.21, 95% CI 0.12−0.39; p < 0.0001); a higher proportion of SA and PL was associated with septate uterus vs. controls (OR 4.29, 95% CI 2.90−6.36; p < 0.0001; OR 2.56, 95% CI 1.52−4.31; p = 0.0004). (ii) treated versus untreated septum: PR and PL were not different in removed vs. unremoved septum(OR 1.10, 95% CI 0.49−2.49; p = 0.82 and OR 0.81, 95% CI 0.35−1.86; p = 0.62); a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.47, 95% CI 0.21−1.04; p = 0.001); (iii) before-after septum removal: the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93−82.13; p < 0.0001) and the proportion of SA and PL was lower after the removal of the septum (OR 0.02, 95% CI 0.02−0.04; p < 0.000 and OR 0.05, 95% CI 0.03−0.08; p < 0.0001) Conclusions: the results show the detrimental effect of the uterine septum on PR, LBR, SA and PL. Its treatment reduces the rate of SA.

Thyroid Dysfunction after Gonadotropin-Releasing Hormone Agonist Administration in Women with Thyroid Autoimmunity.

GnRH agonists (GnRHa) are a useful tool for pretreatment before artificial endometrial preparation for frozen-thawed embryo-transfer (FET). Their prolonged administration has been associated with thyroid dysfunction, both hyper and hypothyroidism. The aim of this study is to investigate the impact of GnRHa administration on thyroid function in women undergoing artificial endometrial preparation. Seventy-eight euthyroid women undergoing endometrial preparation with hormone replacement for FET were retrospectively reviewed. They were divided into two groups according to pretreatment with GnRHa (group A, 42 women) or with an oral contraceptive (group B, 36 women). Group A was subsequently divided into two subgroups according to thyroid autoimmunity presence. Thyroid function has been evaluated and compared among groups and subgroups. Our results did not show any statistically significant differences in age, body mass index, and basal thyroid stimulating hormone (TSH). Total estradiol dosage, duration of treatment, and endometrial thickness were comparable among groups. When TSH was measured 14 days after embryo transfer, no significant differences between the two groups were reported. Among women of group A, TSH was significantly higher only in women with thyroid autoimmunity. GnRHa seems to be associated with thyroid dysfunction in women with thyroid autoimmunity undergoing hormone replacement therapy for FET.

Epigenetics of pregnancy: looking beyond the DNA code.

Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal-fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.

MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining.

PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Role of Renin-Angiotensin-Aldosterone System and Cortisol in Endometriosis: A Preliminary Report.

Endometriosis is a chronic inflammatory disease associated with pelvic pain, infertility, and increased cardiovascular risk. Recent studies suggest a possible role of aldosterone as a pro-inflammatory hormone in the pathogenesis of the disease. Cortisol is also an important mediator of stress reaction, but its role is controversial in endometriosis. The aim of this study was to evaluate aldosterone and cortisol levels and blood pressure values in women with endometriosis. We measured blood pressure, plasma aldosterone, renin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) in 20 women with untreated minimal or mild pelvic endometriosis compared with 20 healthy controls matched for age and body mass index. Aldosterone values were similar in the two groups, while renin was significantly lower and the aldosterone to renin ratio was significantly higher in patients with endometriosis than in controls. Systolic blood pressure was in the normal range, but significantly higher in patients with endometriosis. Morning plasma cortisol was normal, but significantly lower in patients with endometriosis compared with controls, while DHEAS to cortisol ratio was similar in the two groups. These preliminary results are evidence of increased biological aldosterone activity and dysregulation of the hypothalamic-pituitary-adrenal axis in early stages of endometriosis. These alterations could play a role in disease development, suggesting new therapeutic targets for aldosterone receptor blockers.

Clinical Outcomes Deriving from Transfer of Blastocysts Developed in Day 7: a Systematic Review and Meta-Analysis of Frozen-Thawed IVF Cycles.

This meta-analysis aimed to assess the reproductive competence of blastocysts developed on day 7 compared with blastocysts developed on day 5/6. A systematic search was carried out to select relevant studies published before January 2020. Ten retrospective observational cohort studies were included. The primary outcome was the clinical pregnancy rate (CPR). Secondary outcomes were live birth rate (LBR), euploid rate, and survival rates after thawing. Frozen-thawed day 7 blastocyst transfer was associated with a significant reduction in CPR compared to day 5/6 (OR 0.36 95% CI 0.21 to 0.62, p = 0.0002, I2 = 71% and OR 0.43, 95% CI 0.32 to 0.58, p < 0.0001, I2 = 17% respectively). A significantly lower proportion of LBR was found comparing blastocysts transfers in day 7 to those in day 5/6 (OR 0.21, 95% CI 0.16-0.27, p < 0.0001, I2 = 0% and OR 0.34, 95% CI 0.26-0.45, p < 0.0001, I2 = 0% respectively). These findings were confirmed in a subgroup of Preimplantation Genetic Testing for Aneuploidies (PGT-A)-screened blastocysts. Blastocysts biopsied in day 7 was associated with a significant decrease of euploid rate compared with day 5/6 (OR 0.47, 95% CI 0.39-0.57, p < 0.0001, I2 = 69% and OR 0.68, 95% CI 0.61-0.75, p < 0.0001, I2 = 19% respectively). The survival rate after thawing was not statistically different. Sensitivity analyses were also performed. This study shows an association between delayed blastulation and a poorer prognosis in terms of euploid rate and pregnancy outcomes following frozen-thawed transfers. On the other hand, the results do not support the discharge of slow-blastulation embryos.

Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview.

Endometrial cancer (EC) is a deleterious condition which strongly affects a woman's quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.

Sildenafil Supplementation for Women Undergoing Infertility Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The aim of this systematic review and meta-analysis is to summarize data on the effectiveness of Sildenafil supplementation for women undergoing assisted reproduction techniques. This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of Sildenafil administration during infertility treatments compared with a control group in infertile women. Outcomes evaluated were endometrial thickness (ETh) and the clinical pregnancy rate (CPR). The chemical pregnancy rate (ChPR) was also evaluated. Pooled results were expressed as the risk ratio (RR) or mean differences (MD) with a 95% confidence interval (95% CI). Women undergoing ovulation induction who received Sildenafil showed higher ETh and a higher CPR in comparison to controls. In this group, both the ETh and ChPR resulted in significantly higher values only with delayed start administration. Women undergoing fresh or frozen embryo transfer who received Sildenafil showed no significant advantages regarding ETh and CPR in comparison to controls. In this group, we found a significantly higher ChPR in women receiving Sildenafil. A subgroup analysis revealed significant advantages regarding ETh with oral administration for women undergoing fresh or frozen embryo transfer. Sildenafil therapy appears to improve endometrial thickness and pregnancy rate in women undergoing timed intercourses but it resulted not effective in IUI and IVF treatments. Further RCTs with rigorous methodology are still mandatory.