Hormonal rehabilitation of patients with cervical cancer after radical surgical treatment

Radical surgical treatment with and without radiation often induces symptoms of premature menopause in cervical cancer (CC) patients. Few retrospective studies seem to suggest that hormonal replacement therapy (HRT) is not detrimental for patients with CC and can improve life quality in this group of women. To investigate the effect of HRT on menopausal symptoms inpatients with С C history, 85 patients after CC treatment, 22-51 years old, were included into this research. In 59 patients HRT was carried out to overcomepostovariectomic syndrome (POES). Severity of menopausal symptoms, serum estradiol, FSH and lipid profiles were evaluated. The research showed high therapeutic effect as to reducing the frequency of postovariectomic frustration in HRT application. No recurrences of CC were observed in this group of patients. HRT side effects were extremely rare. HRT can effectively cure climacteric symptoms in women with surgical menopause induced by CC treatment.

Late Endocrine Effects after Stem Cell Transplant in a Young Girl with Griscelli Syndrome

Background. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is fatal due to severe immunodeficiency without curative stem cell transplant (SCT). Late endocrinopathies are quite common in other disorders after SCT. These complications have not been reported in GS. Case Presentation. A 7-year-old female presented for growth failure with a history of GS status post curative SCT and consequently developed graft-versus-host disease (GvHD). She also had a history of eosinophilic enterocolitis, for which she was taking supraphysiologic glucocorticoids for the past year. She presented with severe short stature along with mild hyperthyroxinemia with subsequent diagnosis of Graves’ disease, which was treated with methimazole. GH therapy was commenced due to persistent growth failure, with a robust increase in growth parameters. She started spontaneous puberty; however, initial biochemical evaluation revealed hypergonadotropic hypogonadism with undetectable anti-Mullerian hormone (AMH) consistent with low ovarian reserve and premature ovarian failure. Discussion. Growth failure was multifactorial due to her inflammatory condition and poor weight gain from multiple underlying illnesses, including hyperthyroidism, as well as chronic supraphysiologic glucocorticoid use. Although hypothyroidism is more commonly seen after SCT, rare cases of hyperthyroidism have been reported. In addition to SCTs, GvHD and GS have been associated with autoimmune conditions. It is important to monitor pubertal progression as the majority of those treated with alkylating agents prior to SCT have pubertal and ovarian failure and remain at risk for premature menopause.

Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes

Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/ 2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/ D where the risk of OC is elevated beyond our threshold for RRSO. In PALB1, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.

Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats

Introduction: Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit+ cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF). Methods: Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit+ (MACS) and c-Kit- cells (4×105 cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses. Results: POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (P < 0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit+ cells in comparison with POF rats that did not receive these cells (P < 0.05). Compared with the control samples, angiogenesis-related genes, Angpt2 and KDR, showed increased and decreased expressions in POF ovaries, respectively (P < 0.05). c-Kit+ cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (P > 0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit+ cells also restored the reduced fertility rate (P < 0.05). Conclusion: The administration of c-Kit+ cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.

Role of AMH in Prediction of Menopause

Anti-Müllerian Hormone (AMH) is produced by small antral follicles and has evolved over the past three decades as an assumed potential marker of the number of follicles in the human ovaries, also known as ovarian reserve. This quantitative measure, given the gradual decline over time and its non-replenishable feature, could be the dreamed marker for predicting the final exhaustion of ovarian storage: the post-menopause. This introductory chapter summarizes current knowledge with regard to the contribution of serum AMH measurements to predict age of normal menopause and critically discuss its potential in this regard. Furthermore, its predictive role in the context of menopause in association with several frequently occurring fertility disorders such as premature menopause, polycystic ovarian syndrome and endometriosis are discussed. Overall, while ovarian reserve markers including AMH are unmistakably related to age at menopause, they are insufficiently precise to inform on an individual’s journey of ovarian aging.

Spontaneous and Successful Pregnancies After Premature Ovarian Insufficiency: Case Series

Premature ovarian insufficiency (POI) formerly referred to as premature menopause, premature ovarian failure or primary ovarian failure (POF) implies quantitative and qualitative alterations in the functional integrity of the ovarian follicles leading to irregularity of menses, clinical manifestations of signs and symptoms of menopause and impaired fertility performance. This phenomenon tends to occur in about 1% of the women population in their reproductive years and arbitrarily below the age of 40 years. We hereby present case series of seven subjects who were specifically complaining of infertility or low fertility from a total of 242 women with presumed diagnosis of premature ovarian insufficiency. These were extracted from a pool of 10,090 clients that were documented over a year’s period i.e. from January 1, 2020 up to December 31, 2020. Our patients achieved spontaneous pregnancies and underwent a normal course of the pregnancies that culminated in uneventful childbirths. The deliveries invariably took place in private setups. We maintained a close contact telemetrically and physically; and followed them up during their course of the delivery and the postpartum period since they were denoted as very high risk pregnancy. To the best of our knowledge, there is no isolated similar case report or publication in the Ethiopian setting. The objective of the case series presentation is linked with the intention of adding to the world literature highlighting its relevance, desire to create more awareness and establish the basis for further inspiration to develop future undertakings in the understanding of diminished ovarian reserve vis-a-vis premature ovarian insufficiency and spontaneous pregnancy.