Primary amenorrhoea - cytogenetic study in 40 Indian women.

BACKGROUND: Primary amenorrhoea (PA) refers to an ailment when adolescent girls do not attain menarche naturally. It is one of the most common gynaecological disorders specified. Chromosomal abnormalities play a pivotal role in PA. Cytogenetic analysis is an indispensable diagnostic tool to determine the abnormality of the chromosome. In an emerging country like India, cytogenetic analysis is at a nascent stage. There are very few studies on Cytogenetics present in eastern India, including West Bengal. In rural and suburban areas PA sufferers often experience late diagnosis and struggle to access suitable curative management. The aim of the study is to evaluate the various types of chromosomal abnormalities in patients suffering from PA for accurate, better management of the same and further counselling. METHODS: A total of 40 PA cases were referred by obstetricians and gynaecologists to the Department of Genetics of Nirnayan Health Care, Kolkata. To screen the chromosomal abnormalities, human leukocyte culture was accomplished with their peripheral venous blood followed by G-banding and then karyotyping was executed according to ISCN-2020. RESULT: Out of 40 patients, 29 were normal among which 46,XX was found in 70% cases (n = 28) and 46,XX,9qh + in 2.5% (n = 1). The remaining 11 showed different types of abnormalities. 45,X was found in 10% (n = 4), 46,X,i(X)(q10) in 2.5% (n = 1), 46,X,del(X)(p11.2) in 2.5% (n = 1), 46,X,del(X)(p22.1) in 2.5% (n = 1), 46,X,del(X)(q24) in 2.5% (n = 1), 46,XY in 2.5% (n = 1), mos 45,X[22]/46,Xi(X)(q.10)[8] in 2.5% (n = 1) and mos 45,X[16]/46,XY[14] (2.5%) in 2.5% (n = 1). CONCLUSION: This study indicates the importance of chromosomal study which must be included in early diagnosis of PA. Karyotyping at the appropriate phase of life will not only help in the judicial management of this disorder but will also give young girls a better lifestyle.

Primary amenorrhoea is a common gynecological disorder reported in adolescent girls, often linked to chromosomal abnormalities. In Eastern India, including West Bengal, where cytogenetic analysis is still in its nascent stage, late diagnosis and limited access to curative management are prevalent issues. A study conducted from January 2021 to May 2023 at Nirnayan Healthcare, Kolkata aimed to evaluate chromosomal abnormalities in 40 PA cases. Out of these, 28 exhibited normal karyotypes (46,XX); one patient was reported with 46,XX,9qh + which is considered a normal karyotype, while the remaining 11 revealed diverse abnormalities, including 45,X; sex reversal & several structural variations. The study underscores the significance of cytogenetic analysis in the early diagnosis of Primary Amenorrhoea. Early karyotyping not only facilitates judicious management but also ensures a better lifestyle for affected girls.

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Vaginoplasty with Amnion Graft: Management of Mayer-Rokitansky-Kuster-Hauser Syndrome.

Mayer-Rokitansky-Kuster-Hauser syndrome also known as mullerian agenesis is a rare congenital condition in which there is absence of uterus along with upper vagina. Patient usually presents with primary amenorrhea with or without cyclical lower abdominal pain but have normal secondary sexual characters. Modified McIndoe Vaginoplasty with amnion graft is the commonest surgery performed worldwide. A 23 year old girl with normal secondary sexual characters presented with primary amenorrhea with cyclical lower abdominal pain; on examination blind vagina was present. Vaginoplasty with amnion graft was done and vaginal mould was placed. Vaginal dilatation with Hegar's dilator was done weekly until 6 weeks. She is under regular follow-up at present and advised for regular manual dilation at home. McIndoe Vaginoplasty with amnion graft is a simple yet rewarding procedure especially in low resource countries like ours, with good success rate and with minimal postoperative complications. Keywords: Amnion graft; Mayer-Rokitansky-Kuster-Hauser Syndrome; Modified McIndoe Vaginoplasty; Primary amenorrhea; Secondary sexual characters.

Primary Amenorrhea and Premature Ovarian Insufficiency.

This review focuses on primary amenorrhea and primary/premature ovarian insufficiency due to hypergonadotropic hypogonadism. Following a thoughtful, thorough evaluation, a diagnosis can usually be discerned. Pubertal induction and ongoing estrogen replacement therapy are often necessary. Shared decision-making involving the patient, family, and health-care team can empower the young person and family to successfully thrive with these chronic conditions.

Heavy menstrual bleeding in women with inherited bleeding disorders in use of LNG-IUS: A systematic review and single-arm meta-analysis.

OBJECTIVES: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss. STUDY DESIGN: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding. RESULTS: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%). CONCLUSION: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding. IMPLICATIONS: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women.

Impact of Secondary Amenorrhea on Cardiovascular Disease Risk in Physically Active Women: A Systematic Review and Meta-Analysis.

BACKGROUND: Exercise-associated secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's normal cardioprotective pathways. Estrogen may be essential in a woman's endothelial adaptations to exercise. The objective of this review was to assess the association between secondary amenorrhea in physically active women and cardiovascular disease (CVD) risk. METHODS AND RESULTS: A literature search was performed in January 2023 and updated in August 2023 of the Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Citation chaining was done to screen for additional studies. Eight sources were searched for gray literature. Studies that compared physically active women with amenorrhea to physically active women with eumenorrhea aged 18 to 35 years with evidence of CVD, alterations to cardiovascular physiology, or CVD risks were included. Eighteen observational studies from 3 countries were included. Overall, the quality of evidence was good. A meta-analysis was performed. Physically active women with secondary amenorrhea had significantly lower estradiol, flow-mediated dilation, resting heart rate, systolic blood pressure, and diastolic blood pressure and higher total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol. CONCLUSIONS: Estrogen deficiency resulting from exercise-associated secondary amenorrhea in physically active women may impact cardiovascular physiology and certain CVD risk factors. The research in this area is observational; therefore, findings should be interpreted cautiously. However, as exercise-associated secondary amenorrhea is reversible and the primary prevention of CVD is important for public health, it may be important to treat secondary amenorrhea and restore estrogen levels.

Girls referred for amenorrhea: analysis of a patient series from a specialist center.

Objective: Among adolescents, amenorrhea is a common reason for medical consultation. Despite the variety of underlying etiologies, the prevalence of the causes is incompletely understood. This study aimed to assess the demographic and etiological factors among patients with amenorrhea treated in a single specialist unit of adolescent gynecology. Design: Retrospective register study. Methods: Medical records of 438 girls evaluated for primary or secondary amenorrhea in a single tertiary care center between 2015 and 2019 were retrospectively reviewed. In all, 423 patients-171 with primary amenorrhea and 252 with secondary amenorrhea-were included in the study. Data on underlying conditions, anthropometric variables, and selected hormonal markers were analyzed. Results: Functional hypogonadotropic hypogonadism was the most frequent reason for primary (56%) and secondary (78%) amenorrhea. It was mostly explained by lifestyle-related functional hypothalamic amenorrhea caused by disordered eating, intense exercise, energy deficiency, psychological stress, and their combinations. Conclusion: Menstrual pattern is a significant indicator of overall health and well-being among adolescent girls and young women. Functional reasons behind primary and secondary amenorrhea are important to recognize. Treatment often requires long-term lifestyle modifications. The frequency of functional causes also implies that most amenorrhea cases are preventable.

Reproductive Planning: Contraceptive Counseling and Nonhormonal Methods.

More than 65% of US women ages 15 to 49 years use contraception every year, many of whom seek care with family medicine. Family physicians are well equipped to provide comprehensive contraceptive counseling to patients in the primary care setting. When discussing options and providing education to patients, clinicians should consider patient preferences, patient autonomy, and adverse effect concerns, and should use a patient-centered approach that upholds the principles of reproductive justice. Nonhormonal methods of contraception include barrier methods and spermicides, fertility awareness-based methods, and (in postpartum individuals) lactational amenorrhea. With barrier methods, spermicides, and fertility awareness-based methods, 13 to 29 out of 100 women may become pregnant. Permanent forms of contraception include female and male sterilization procedures, which are some of the most effective (more than 99% effective) and most commonly used methods in the United States.

Diverse genetic causes of amenorrhea in an ethnically homogeneous cohort and an evolving approach to diagnosis.

RESEARCH QUESTION: Premature ovarian insufficiency (POI) is characterised by amenorrhea associated with elevated follicle stimulating hormone (FSH) under the age of 40 years and affects 1-3.7% women. Genetic factors explain 20-30% of POI cases, but most causes remain unknown despite genomic advancements. DESIGN: We used whole exome sequencing (WES) in four Iranian families, validated variants via Sanger sequencing, and conducted the Acyl-cLIP assay to measure HHAT enzyme activity. RESULTS: Despite ethnic homogeneity, WES revealed diverse genetic causes, including a novel homozygous nonsense variant in SYCP2L, impacting synaptonemal complex (SC) assembly, in the first family. Interestingly, the second family had two independent causes for amenorrhea - the mother had POI due to a novel homozygous loss-of-function variant in FANCM (required for chromosomal stability) and her daughter had primary amenorrhea due to a novel homozygous GNRHR (required for gonadotropic signalling) frameshift variant. WES analysis also provided cytogenetic insights. WES revealed one individual was in fact 46, XY and had a novel homozygous missense variant of uncertain significance in HHAT, potentially responsible for complete sex reversal although functional assays did not support impaired HHAT activity. In the remaining individual, WES indicated likely mosaic Turners with the majority of X chromosome variants having an allelic balance of ∼85% or ∼15%. Microarray validated the individual had 90% 45,XO. CONCLUSIONS: This study demonstrates the diverse causes of amenorrhea in a small, isolated ethnic cohort highlighting how a genetic cause in one individual may not clarify familial cases. We propose that, in time, genomic sequencing may become a single universal test required for the diagnosis of infertility conditions such as POI.

A rare variant of mullerian agenesis: a case report and review of the literature.

INTRODUCTION: Menstruation is a developmental milestone and usually marks healthy and normal pubertal changes in females. Menarche refers to the onset of first menstruation in a female. The causes of primary amenorrhea include outflow tract abnormalities, resistant endometrium, primary ovarian insufficiency, and disorders of the hypothalamus, pituitary, or other endocrine glands. A rare variant of mullerian agenesis, which warrants an individualized approach to management, is presented here. CASE REPORT: We present here the case of a 25-year-old Indian female with pain in the lower abdomen and primary amenorrhea. After a thorough history, clinical examination, imaging, and diagnostic laparoscopy, two small uteri, a blind upper half vagina, bilateral polycystic ovaries, and a blind transverse connection between the two uteri-a horseshoe band cervix-were detected, which confirmed the diagnosis of mullerian agenesis. There was evidence of adenomyosis in the mullerian duct element. This is a rare form of Müllerian abnormality with an unusual presentation. CONCLUSION: Mullerian agenesis is the most common cause of primary amenorrhea with well-developed secondary sexual characteristics. There are various forms of mullerian agenesis. Most of the cases are managed by a multidisciplinary team. Rare variants warrant an individualized approach to management.

Amenorrhea in adolescents using the etonogestrel contraceptive implant.

OBJECTIVE: Clinical factors related to development of amenorrhea in adolescents with the etonogestrel contraceptive implant are not well-understood. The purpose of this study is to describe what baseline clinical characteristics are associated with amenorrhea in adolescents with a contraceptive implant 12 months after placement. STUDY DESIGN: This retrospective cohort study included 252 post-menarchal individuals aged 12-22 years with a contraceptive implant placed between 2016-2020. Data abstracted at insertion, three months post-insertion, and 12 months post-insertion included demographics, baseline bleeding pattern, prior contraception use, post-insertion bleeding pattern, and method discontinuation. We assessed possible predictive characteristics of our outcomes using bivariate and multivariable logistic regression analyses. RESULTS: Twenty nine percent of patients were amenorrheic 12 months after placement. Patients who were amenorrheic at 12 months were more likely to be obese (41.1% vs 24.6%, p = 0.01), to have been amenorrheic prior to implant insertion (16.9% vs 5.4%, p < 0.01, to have used hormonal contraception immediately prior to insertion (42.5% vs 26.3%, p = 0.01), to have had the most recent contraceptive method being another implant (12.3% vs 3.6%, p = 0.02), and to have developed amenorrhea within three months after placement (22.2% vs 12.6%, p < 0.01). After multivariable regression analysis, only obesity (adjusted odds ratio [aOR] 2.2 95% CI 1.1-4.2) and amenorrhea at three months (aOR 3.6, CI 1.1-11.5) were associated with amenorrhea at 12 months. CONCLUSION: Obesity and early amenorrhea were associated with 12-month amenorrhea in adolescents using the etonogestrel subdermal implant. Understanding this can help with contraceptive method selection and counseling for patients and providers. IMPLICATIONS: Obesity and early amenorrhea with the etonogestrel contraceptive implant are associated with longer-term amenorrhea in adolescents using this method. These findings can aid providers with method selection and pre-insertion decision-making for adolescents considering contraceptive implant use, as well as continued counseling after placement.

Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.

INTRODUCTION: Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens. PATIENT CONCERNS: We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone. DIAGNOSIS: The ovarian tumors had hormonal activity. INTERVENTIONS: The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments. OUTCOMES: Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence. CONCLUSION: The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.

[Endocrine and psychosomatic disorders in patients with amenorrhea].

The article presents data on the relationship of pathogenetic mechanisms for the development of menstrual disorders of functional and organic origin in connection with mental disturbances from the point of view of the psychosomatic concept. According to the latter, functional disorders of the menstrual cycle are considered as psychosomatic, in which gynecological pathology develops as a result of psychopathological illness. A striking example of such a disorder is functional hypothalamic amenorrhea. At the same time, endocrinopathies, such as polycystic ovary syndrome and premature ovarian insufficiency, can also be considered in the paradigm of psychosomatic illnesses of ovarian function due to the high prevalence of anxiety and depressive disorders in this cohort of patients. This review highlights the importance of interdisciplinary collaboration between a gynecologist and a psychiatrist for the most effective reproductive rehabilitation of patients with amenorrhea. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2018 to 2023.However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1985.

The impact of COVID-19 on menstrual cycle's alterations, in relation to depression and sleep disturbances: a prospective observational study in a population of medical students.

BACKGROUND: The sars-Cov-2 pandemic has determined psychological stress, particularly in the young population of medical students. We studied the impact of the pandemic on menstrual cycle alteration in relation to psychological stress, presence of depression, sleep disturbances and post-traumatic stress, on a population of medical students. METHODS: 293 female students at the Faculty of Medicine and Psychology of the Sapienza University of Rome (23.08 years old ± 3.8) were enrolled. In March 2021, one year after quarantine, a personal data sheet on menstrual cycle, examining the quality of the menstrual cycle during the pandemic, compared to the previous period. Concomitantly, the Beck Depression Inventory and the Impact of Event Scale have been administered. A Pearson chi-square test was assessed to evaluate the difference between the characteristics of the menstrual cycle and the scores obtained with the questionnaires. RESULTS: A statistically significant association between menstrual alterations and stress during pandemic had been found. The onset of depressive symptoms and sleep disturbances was observed in 57.1% and in 58.1% of young women with cycle's alterations, respectively. Amenorrhea was three times more common in female students with depressive symptoms, premenstrual syndrome had a significant correlation with both depression and sleep disturbances. The pandemic has been related to menstrual alterations, with depressive symptoms and sleep disorders. Amenorrhea is connected to depression, as observed on the functional hypothalamic amenorrhea. CONCLUSIONS: The pandemic affected the menstrual cycle as well as the depressive symptoms and sleep. Practical implications of the study lead to the development of strategies for psychological intervention during the pandemic experience, in order to help medical trainees, with specific attention to women's needs. Future studies should analyze the impact of other types of social stress events, on sleep, depression and the menstrual cycle beside the pandemic.

[Analysis of a child with 46,XY Disorder of sex development due to a novel variant of NR5A1 gene].

OBJECTIVE: To analyze the clinical features and genetic basis of a child with Disorder of sex development (DSD). METHODS: A child who was admitted to the Linyi People's Hospital for primary amenorrhoea on July 29, 2019 was selected as the study subject. Clinical data of the child was collected. Chromosomal karyotyping and quantitative real-time PCR were used to detect Y chromosome microdeletions and other chromosomal aberrations. Next-generation sequencing was carried out for the child and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old girl, has featured primary amenorrhoea and onset of secondary sex characteristics of males. Ultrasound exam had detected no uterus and definite ovarian structure, but narrow band vaginal hypoecho and curved cavernoid structure. The child was found to have a 46,XY karyotype without an AZF deletion. DNA sequencing revealed that she has harbored a maternally derived c.323delA (p.Q108Rfs*188) variant in the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene, which may result in a truncated protein. The variant was classified as pathogenic (PVS1+PM2_Supporting+PP4) based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The NR5A1: c.323delA variant probably underlay the pathogenesis of 46,XY DSD in this child. The discovery of the novel variant has enriched the mutational spectrum of the NR5A1 gene and provided a basis for clinical diagnosis, treatment and prenatal diagnosis.

One-third of amenorrheic transmasculine people on testosterone ovulate.

Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy. Histological signs of recent ovulatory activity, including the presence of ovulatory follicles, corpus luteum, and corpus albicans, are observed in 17 of 52 individuals (33%). This is not significantly correlated to the duration, testosterone serum levels, or type of testosterone used. These results suggest that amenorrhea does not equal anovulation in transmasculine people on adequate testosterone therapy, emphasizing the importance of contraception for people who engage in sexual activity that can result in pregnancy.