Spontaneous Menstruation Research Articles

Performance of the MiniMed 780G system on mitigating menstrual cycle-dependent glycaemic variability.

To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle. A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed-loop (AHCL) period; each period lasted 3 consecutive months. During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P < .01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P < .01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P = .72), without increasing the time spent below 70 mg/dL (P > .05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P < .01), during the luteal phase. The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle-dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle.

Analysis of the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea

Objective: To investigate the effects of eating and emotions on reproductive axis function in patients with functional hypothalamic amenorrhea (FHA). Methods: A retrospective cohort study was conducted to summarize the clinical and endocrine characteristics of 58 patients with FHA at initial diagnosis and to follow up the recovery of ovulation and spontaneous menstruation in the patients to investigate these biochemical indicators and their effects on recovery outcomes. Results: Among patients with FHA, 13.8% (8/58) and 15.5% (9/58) had above moderately severe depressive and severe anxiety symptoms respectively, and 25.9% (15/58) were at high risk for eating disorders. 34.5% (20/58) were included assessed as having recovered. The non-recovered group had higher scores on the Patient Health Questionnaire (PHQ-9) (p = .022) and higher scores on the Eating Attitude Test-26 (EAT-26) (p = .03) as well as bulimia and food preoccupation (p = .041). Follicle diameter >5 mm at initial diagnosis was an independent factor influencing recovery of reproductive axis function (odds ratio = 7.532; 95% confidence interval, 1.321–42.930; p = .023). Conculsions: Mood disorders and a certain risk of eating disorders were present in FHA.These, together with weight loss, endocrine and follicle size, could influence the outcome.

P-709 A retrospective cohort study of the stability of ovarian reserve in women with Turner Syndrome (TS) and spontaneous menstruation

Abstract Study question What is the stability of ovarian reserve, as measured by anti-Müllerian hormone (AMH), over time in women with TS and spontaneous menstruation beyond age 16? Summary answer Ovarian reserve, as measured by AMH, is stable over time in adult (&amp;gt;16 years) women with TS and spontaneous menstruation. What is known already TS is associated with gonadal dysgenesis and premature ovarian insufficiency (POI). In a minority of TS women, ovarian function is maintained with ongoing menstruation and the possibility of achieving spontaneous pregnancy. There is uncertainty as to the role of fertility preservation in this population. The 2016 Clinical practice guidelines for the care of girls and women with TS recommend counselling women with TS that their probability to conceive spontaneously decreases rapidly with age. However, the natural history of AMH over time in this sub-population has not been reported. Study design, size, duration Retrospective cohort study of patients attending the TS clinic at University College London Hospital between December 2020 and December 2022. This time interval was chosen to ensure that the entire UCLH TS cohort was screened, even if one year of annual follow-up was missed during COVID-19. Clinical records were reviewed to identify adult patients (&amp;gt;16years old) with spontaneous menstruation at any time and at least one measurement of AMH. Participants/materials, setting, methods To assess the stability of the AMH values, the rate of change was calculated using the formula: ratechangeAMH = (lastAMH-baselineAMH)/(time in months between readings). The distribution of the rate of change in the PCOS and non-PCOS groups was then compared using a non-parametric Mann-Whitney test: a regression analysis was performed with the outcome as the ratechangeAMH and the explanatory variables being baseline AMH and age at baseline AMH. Main results and the role of chance 55 patients were identified, median age 25.9 (range 16 to 41).Their karyotypes were 45X (n = 2) 45X/46XX mosaic (n = 28), 45X/47XXX mosaic (n = 11), and other (n = 14). The number of AMH measurements varied from 1-10 and the longest duration of AMH follow-up was 11 years. A subgroup of 9 patients met diagnostic criteria for PCOS. Median AMH for the 45X/46XX group was 21.25pmol/L (range 0.45-59.36), for the 45X group the median was 1.39pmol/L (range 0.20-2.57), in the 47XXX mosaic group the median was 5.05pmol/L (range 0.70-13.97) and in the other group the median was 9.35pmol/L (0.20-54.40). There was a significantly higher mean AMH, adjusted for age and baseline AMH, in the PCOS group than non PCOS group, mean 26.83 vs 16.23 pmol/L (p &amp;lt; 0.01). Overall, the mean rate of change of AMH was +0.0386pmol/L per month 95%CI [-0.0454, +0.1227] and the median was 0.0000pmol/L per month. In the PCOS group, the mean rate of change was +0.0034 pmol/L per month, median 0.0000pmol/L per month. Regression analyses determined that neither age or baseline AMH had a significant impact on the rate of change. Only one patient in the cohort went onto develop POI during the period of follow up. Limitations, reasons for caution The average age of this cohort at the end of the reported follow up period is 25.9. Ongoing prospective follow up is needed to assess the stability of ovarian reserve into the later part of the typical reproductive window to confirm ongoing stability and assess age reated decline. Wider implications of the findings These findings question the necessity and efficacy of fertility preservation in this subset of TS patients as ovarian reserve is stable over time. Until further data is available, we advocate offering observation with annual AMH masurement rather than immediate recourse to fertility preservation. Trial registration number Not applicable

Unification and orificing of two functional noncommunicating uterine horns through the created neovagina using peritoneum

ObjectiveTo demonstrate the surgical approach for Müllerian agenesis with bilateral uterine remnants containing functional endometrium. DesignStepwise demonstration of the technique with narrated video footage SettingA Tertiary University Hospital, Reproductive Surgery Unit. PatientAn 18-year-old adolescent was admitted to a tertiary university hospital with complaints of primary amenorrhea and cyclic pelvic pain. Physical examination and MRI scans suggested a complex Müllerian abnormality. The patient had uterine remnants with bilateral functional endometrium and cervico-vaginal agenesis. InterventionAn operation was planned to reconstruct her anatomy by providing a neovagina and anastomosing the uterine remnants. GnRH analogs were prescribed to suppress her menstruation until the procedure. The operation was performed in the third month after the initial diagnosis. A laparoscopy was conducted, revealing approximately 5x6 cm bilateral uterine horns with healthy adnexa.As the first step, a neovagina was created using a modified peritoneal pull-down technique, a standard approach in our clinic. A vaginal incision was made, and a blind vaginal dissection was performed to reach the peritoneum vaginally. Subsequently, an acrylic vaginal mold was inserted. The vaginal orifice was laparoscopically incised using ultrasonic energy with guidance from the inserted vaginal acrylic mold. The orifice was gradually dilated with larger molds. The entire pelvic peritoneum was dissected circularly, and the distal part of the dissected peritoneum was pulled down using four 2.0 Vicryl sutures at 0, 90, 180, and 270 degrees from the opened vaginal orifice. The uterine cavities of both remnants were incised, and two separate Foley catheters were placed in both cavities. A mold with a hole was used to insert the catheters through the vagina. Both catheters were secured in the cavities with Prolene sutures pulled up from the anterior abdominal wall.The next step involved uterine anastomosis. The uterine remnants were unified through continuous suturing, resulting in the formation of a normally shaped uterus. In the final step, the created uterus and neovagina were anastomosed. The patient received instructions on how to perform mold exercises and follow-up care. Main Outcome MeasureDescription of a laparoscopic management of a rare mullerian abnormality. ResultsThe postoperative MRI scan at one month revealed healed unified uterine cavities and vagina. The patient experienced spontaneous menstruation in the second month after surgery and now maintains regular menses with an approximately 9-10 cm functional vagina. Within three months after surgery, the VAS (visual analog scale) scores for chronic pelvic pain and dysmenorrhea decreased from 9 to 2-3. ConclusionsMüllerian abnormalities are exceptionally rare, and their spectrum is broad, making it challenging to identify an exact surgical method to restore functional anatomy. Therefore, a customized surgical approach should be designed for each patient based on their unique condition.

Analysis of the benefit of gonadotropin-releasing hormone agonist treatment in premenopausal women undergoing hematopoietic cell transplantation

Gonadotropin-releasing hormone agonist (GnRHa) appears to exhibit ovarian protection during chemotherapy for malignant tumors. The purpose of this study was to analyze the benefits of GnRHa in premenopausal women undergoing hematopoietic cell transplantation (HSCT). Candidates for myeloablative chemotherapy HSCT requiring fertility preservation in the Gynecological Endocrinology Clinic of Peking University People’s Hospital from December 2011 to December 2021 were retrospectively analyzed. Patients who chose to receive GnRHa treatment were given at least 2 courses of a 3.75-mg dose of a GnRHa before myeloablative chemotherapy, and patients who chose not to receive GnRHa treatment were included in the control group. All patients were monitored for menstruation return and menopause-related symptoms, and ovarian function tests [follicle-stimulating hormone (FSH), luteinizing hormone, and estradiol] were performed 6–12 months after HSCT. In addition, we assessed the vaginal bleeding of patients in the laminar air-flow room (LAFR). A total of 234 cases were included in this study: 77 cases in the treatment group and 157 cases in the control group. The incidence of vaginal bleeding in the LAFR in the treatment group was significantly lower than that in the control group (24.68% vs. 79.62%, P < 0.001). The menopausal symptoms of the patients in the treatment group were reduced after transplantation (46.75% vs. 19.75%, P < 0.001). There was no difference in visible follicles by follow-up ultrasound in the two groups after HSCT (16.88% vs. 13.38%, P = 0.474). The level of FSH at 6–12 months after transplantation was lower (98.00 mIU/ml vs. 117.53 mIU/ml, P = 0.001). The proportion of patients with FSH < 40 mIU/ml did not differ between the two groups. One patient in the treatment group recovered spontaneous menstruation, while none recovered spontaneous menstruation in the control group (1.30% vs. 0%, P = 0.329). The use of GnRHa may relieve menopause-related symptoms and reduce vaginal bleeding in the LAFR and breakthrough bleeding after transplantation. GnRHa treatment can reduce the level of FSH after myeloablative chemotherapy, but it cannot reduce the incidence of premature ovarian failure in women of reproductive age following myeloablative HSCT.

Population-Based Characterization of Menstrual Migraine and Proposed Diagnostic Criteria

There is a need for better recognition and more extensive research into menstrual migraine (MM) in the general population, and a revision of the diagnostic criteria for MM is warranted to move the field forward. Increased understanding of MM is crucial for improving clinical care, diagnosis, and therapy for MM. To assess the clinical characteristics of MM, including severity and treatment response, and to propose new diagnostic criteria for pure MM and menstrually related migraine. This is a case-control study of Danish individuals with migraine. All individuals completed a 105-item validated diagnostic migraine questionnaire, sent via the Danish electronic mailing system (e-Boks) between May and August 2020, allowing diagnosis of pure MM and menstrually related migraine by the International Classification of Headache Disorders, Third Edition (ICHD-3). Data analysis was performed from September 2021 to November 2022. Diagnosis of migraine. Clinical characteristics of women with MM and women with nonmenstrual migraine (non-MM) were compared using the ICHD-3 diagnostic criteria. A simulation of the risk of randomly misclassifying MM was based on number of migraine attacks during 3 menstrual cycles (3 × 28 days), and simulation analyses were performed using 100 000 permutations of random migraine attacks in migraine patients. A total of 12 618 individuals, including 9184 women, with migraine participated in the study. Among the women with migraine, the prevalence of MM was 16.6% (1532 women), and the prevalence of non-MM was 45.9% (4216 women). The mean (SD) age was 38.7 (8.7) years for women with MM and 37.0 (9.2) years for women with non-MM. Of the 1532 women with MM, 410 (26.8%) fulfilled ICHD-3 diagnostic criteria for pure MM, 1037 (67.7%) fulfilled ICHD-3 diagnostic criteria for menstrually related migraine, and 152 (9.9%) fulfilled proposed diagnostic criteria for rare pure MM. MM was associated with a higher frequency of migraine-accompanying symptoms (odds ratio [OR], 1.98; 95% CI, 1.71-2.29), more frequent (OR, 7.21; 95% CI, 5.77-9.03) and more severe (OR, 1.17; 95% CI, 1.13-1.21) migraine attacks, lower frequency of nonmigraine headache (OR, 0.31; 95% CI, 0.18-0.49), an overall greater response to treatment with triptans (OR, 1.66; 95% CI, 1.24-2.24), better improvement of migraine attacks during late pregnancy (OR, 5.10; 95% CI, 2.17-14.00), and faster reappearance of migraine attacks post partum (OR, 3.19; 95% CI, 2.40-4.25). Hormonal contraceptive-related MM was associated with a higher prevalence of migraine without aura than migraine related to spontaneous menstruation (OR, 1.82; 95% CI, 1.62-2.06). Otherwise, no differences between hormonal and spontaneous MM were observed. The risk of random diagnostic misclassification of ICHD-3 menstrually related migraine in women with high frequency episodic migraine was 43%. This risk was reduced to 3% when applying the proposed criteria for menstrually related migraine. In this case-control study, MM in the general population had clinical characteristics that were quantitively different from those of non-MM. Detailed descriptive data and suggested improved diagnostic criteria for pure MM and menstrually related migraine were provided.

Age and menstrual cycle may be important in establishing pregnancy in female athletes after retirement from competition

ABSTRACT Background Although it has been shown that amenorrhea associated with low energy availability or relative energy deficiency in sport affects body physiology in female athletes, the association between menstrual dysfunction during active sports careers and reproductive function after retirement is not clear. Objective To investigate the association between menstrual dysfunction during their active sports career and post-retirement infertility in female athletes. Methods A voluntary web-based survey was aimed at former female athletes who had become pregnant and gave birth to their first child after retirement. Nine multiple-choice questions were included, on maternal age, competition levels and menstrual cycles during active sports careers, time from retirement to pregnancy, the time of resumption of spontaneous menstruation after retirement, conception method, and mode of delivery, etc. Regarding cases of primary and secondary amenorrhea among the abnormal menstrual cycle group, only those whose spontaneous menstruation had not recovered from retirement to the time of pregnancy were included in the study. The association between the presence of abnormal menstrual cycles from active sports careers to post-retirement pregnancy and the implementation of infertility treatment was evaluated. Results The study population included 613 female athletes who became pregnant and gave birth to their first child after retiring from competitive sports. Of the 613 former athletes, the infertility treatment rate was 11.9%. The rate of infertility treatment was significantly higher in athletes with abnormal than normal menstrual cycles (17.1% vs. 10.2%, p = 0.0225). Multivariable logistic regression analysis showed that maternal age (adjusted odds ratio [OR] 1.194; 95% confidence interval [CI] 1.129, 1.262) and abnormal menstrual cycles (OR and 1.903; adjusted OR 1.105, 3.278) were the relevant factors for infertility treatment. Conclusion It was suggested that menstrual dysfunction that persist from active sports careers to post-retirement may be a factor in infertility when trying to conceive after retirement.

Atypical Swyer Syndrome Presenting with Spontaneous Breast Development and Secondary Amenorrhea

46, XY pure gonadal dysgenesis (Swyer syndrome) is usually presented as sexual infantilism with delayed puberty and primary amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A 32-year-old woman complained of secondary amenorrhea lasting 1 year. Her menarche occurred at the age of 15. On physical examination, her external genitals were completely feminine. Breast development and pubic hair were compatible with Tanner stage V. Pelvic ultrasound showed a small-sized uterus and gonads. Laboratory investigations revealed follicle-stimulating hormone (FSH) 75.86 mIU/mL, estradiol 28.67 pg/mL, testosterone 0.27 ng/mL, dehydroepiandrosterone sulfate (DHEAS) 260.55 ug/dL and anti-Müllerian hormone (AMH) &lt; 0.02 ng/mL. Chromosomal analysis indicated a 46, XY karyotype. She underwent laparoscopic gonadectomy, and pathology revealed dysgenetic gonads without germ cell tumors. Only a few cases of Swyer syndrome, spontaneous breast development or spontaneous vaginal bleeding related with germ cell tumor have been reported in the literature. To my knowledge, this is the first report of Swyer syndrome with unexplained spontaneous breast development and menstruation, despite the absence of hormone-producing gonadal neoplasm.

Reproductive prognosis of patients with hypogonadotropic hypogonadism: Retrospective review of 16 cases with amenorrhea.

The aim of this study was to evaluate the general characteristics, menstruation status, and fertility outcomes of patients with hypogonadotropic hypogonadism (HH). We evaluated 16 patients with HH who visited our institution between April 2012 and March 2016 with a complaint of amenorrhea. Four (25%) patients had primary amenorrhea and the remaining 12 (75%) cases had secondary amenorrhea. Among the patients with primary amenorrhea, weight loss was considered to be the underlying cause in one (25%) patient, whereas the remaining three (75%) cases were idiopathic HH. Among HH cases with secondary amenorrhea, six (50%) developed amenorrhea following weight loss, whereas the remaining six cases were of unknown etiology. Among the 16 patients with HH, we observed the sporadic restart of the menstrual cycle in four (25%) women during follow-up. Infertility treatment was administered to nine patients with HH who wished to become pregnant. Clomiphene citrate was effective in four patients with secondary amenorrhea and induced follicular development. Seven of nine patients with HH (77.8%) became pregnant following infertility treatment. In some cases of HH, the serum levels of gonadotropin increased sporadically during follow-up, regardless of the recovery of menstruation. We followed one patient with HH for more than 20 years. Although her gonadotropin levels were generally low and sometimes fluctuated without spontaneous menstruation, they increased dramatically to menopausal levels at 50 years of age. However, they again decreased to hypogonadotropic levels. As the pathophysiology varied widely among patients, the etiologic factors underlying HH might also vary.

Survey of changes in ovarian and uterine artery blood flow and indexes by transvaginal Doppler sonography in POI patients and effect of acupuncture on their fertility

Background: Primary ovarian insufficiency (POI) is a common cause of infertility and usually defined by the triad of amenorrhea, estrogen deficiency, and elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in women &lt; 40 years of age. The aim of the present study was to investigate the relationship between uterine and ovarian blood flow with acupuncture and fertility ratio in patients of the Firoozgar Hospital Infertility Clinic. Methods: Twenty-nine patients with POI were included in this clinical trial. FSH, LH, estradiol (E2), and anti-Müllerian hormone (AMH) levels were measured. Patients with Turner syndrome were identified and excluded from the study. Selected patients were evaluated using transvaginal color Doppler sonography used to measure ovarian volume, endometrial thickness, flow rates, and uterine and ovarian artery indexes. Patients were treated with acupuncture twice a week for 5 weeks. After the end of treatment, hormonal assays and an ultrasound examination were repeated to check the changes. Results: Indexes of the uterine arteries (Resistance Index, Pulsatility Index) before versus after the intervention were significantly different (P &lt; 0.00) and uterine vascularity increased after treatment in 22 patients (75.8%). LH and FSH hormone levels were significantly decreased after the intervention (P &lt; 0.00), while AMH and E2 levels were significantly increased after treatment (P &lt; 0.00). The post-intervention right ovarian reserve was significantly increased (P = 0.02), whereas there was no significant difference in left ovarian reserve before vs. after treatment (P = 0.39). Spontaneous menstruation was detected after acupuncture in 16 patients. Conclusions: Our study demonstrated changes in vascularity, hormone levels, menopausal symptoms, and menstrual induction in patients after acupuncture intervention. Keywords: POI, acupuncture, arterial indexes.

Follicular development during hormone replacement therapy in patients with premature ovarian insufficiency.

PurposeTo provide information about the relationship between follow‐up period and follicular development in patients with infertility due to premature ovarian insufficiency (POI) who are undergoing hormone replacement therapy (HRT). It is necessary to detect follicle development for artificial insemination or in vitro fertilization.MethodsThis retrospective cohort study was conducted at a university hospital in Tokyo, Japan, from April 2014 to February 2019 in 20 patients [follicular development group, 11 women (55%); non‐follicular development group, 9 women (45%)] with POI; their follicular development was followed up weekly. Background characteristics, including age, follicle‐stimulating hormone (FSH) and anti‐Mullerian hormone levels (AMH), the period from the last spontaneous menstruation to hormone replacement therapy initiation, and follow‐up period during HRT were investigated. The period without follicular development was tabulated, and the subsequent cumulative follicular development detection rate was calculated.ResultsAt least 1‐year follow‐up, the cumulative follicular development rate was 70%; follicular development was observed with a probability of 49.1% at 3 months, 33.4% at 6 months, and 8.3% at 12 months in the follow‐up period.ConclusionsThe results show that the longer the non‐follicle development period, the lower the probability of subsequent follicular development in patients with POI during HRT.

Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI).

Premature ovarian insufficiency (POI) occurs in at least 1% of all women and causes life-long health problems and psychological stress. Infertility caused by POI used to be considered absolute, with infertility treatment having little or no value. Generally, it has been thought that medicine can provide little service to these patients. The etiology of POI has been found to be genetic, chromosomal, and autoimmune. In addition, the increasing numbers of cancer survivors are candidates for iatrogenic POI, along with patients who have undergone ovarian surgery, especially laparoscopic surgery. Over 50 genes are known to be causally related to POI, and the disease course of some cases has been clarified, but in most cases, the genetic background remains unexplained, suggesting that more genes associated with the etiology of POI need to be discovered. Thus, in most cases, the genetic background of POI has not been clarified. Monosomy X is well known to manifest as Turner’s syndrome and is associated with primary amenorrhea, but recent studies have shown that some women with numerical abnormalities of the X chromosome can have spontaneous menstruation up to their twenties and thirties, and some even conceive. Hormone replacement therapy (HRT) is recommended for women with POI from many perspectives. It alleviates vasomotor and genitourinary symptoms and prevents bone loss and cardiovascular disease. POI has been reported to reduce quality of life and life expectancy, and HRT may help improve both. Most of the problems that may occur with HRT in postmenopausal women do not apply to women with POI; thus, in POI, HRT should be considered physiological replacement of estrogen (+progesterone). This review describes some new approaches to infertility treatment in POI patients that may lead to new treatments for POI, along with the development of more sensitive markers of secondary/preantral follicles and genetic diagnosis.

Hydrocortisone as a Potential Treatment of Savage Ovary Syndrome: A Rare Case from Syria

Advances in Medical, Dental and Health Sciences,2020,3,3,49-51.DOI:10.5530/amdhs.2020.3.12Published:October 2020Type:Case ReportAuthors:Dema Adwan Author(s) affiliations:Dema Adwan* Damascus University Gynecology and Obstetrics Hospital, SYRIA. Abstract:A 32-year old woman with a secondary amenorrhea for 5 years presented to my clinic (April 2019), previously had been treated as a premature ovarian failure patient and put on HRT. With further investigation, FSH Levels were high at the menopausal range, whereas the AMH levels and antral follicles count were within normal ranges and found to be age-compatible, These findings, as well as the failure of ovaries to respond to exogenous gonadotropins, helped to set the diagnosis of Savage Ovary Syndrome, which is also known as Insensitive Ovary Syndrome (IOS). Written informed consent was obtained from the patient for publication of this case report and accompanying images" Patient was convinced to be treated empirically with a high dose of Hydrocortisone and the result was the patient well responded as a normal spontaneous menstruation happened. The analysis of FSH and estradiol induces normal values and the return of the functional activity of the ovary to the formation of multiple ovarian bilateral follicle and give an echo feature similar to the ovarian hyper stimulatory syndrome with an increase the thickness of the endometrium. This case shows the importance of further studying patients with secondary amenorrhea and high levels of gonadotropins and not to treat them all as premature ovary insufficiency patients, just like our patient was firstly treated for a long time. Furthermore, the case highlights the potential benefit of the treatment of Savage Ovary Syndrome patients with Hydrocortisone. Keywords:Antral follicles, Gonadotropin, Infertility, Insensitive ovary, Resistant ovarian syndrome, Secondary amenorrheaView:PDF (535.52 KB)

Effect of transdermal estradiol therapy on bone mineral density of amenorrheic female athletes.

The effects of transdermal estradiol treatment (HT) in amenorrheic athletes (AA) with low body weight (BW) and low bone mineral density (BMD) are unknown. To investigate whether HT increases BMD in AA with low BW and to compare the results with levels in AA who have recovered spontaneous menstruation (SM). Female athletes (n=151) were recruited at the Japan Institute of Sports Sciences and the University of Tokyo. All participants were divided into four groups: an AA group (untreated group) (n=36), a HT group (n=55), a SM group (n=21), and an eumenorrheic athletes (EA) group (n=39). Height, body weight, blood tests, and dual-energy X-ray absorptiometry were measured at baseline and after 12months. The HT group was treated daily for 12months with transdermal estrogen therapy. In addition, participants received oral progestin for 7days once every 3months. After 12months, BMD in the AA group was significantly lower than at baseline; however, BMD in the other three groups was significantly higher than at baseline. The ratio of the change in BMD values before and after 12months was -1.6±3.2% for the AA group, 5.3±8.7% for the HT group, 11.1±8.9% for the SM group, and 2.3±5.7% for the EA group. The rate of change in BMD values in the SM group was greater than that in the HT group. HT increased BMD in AAwith low BW, and the increase in those with SM was greater than that in those treated with HT.

Characteristics of the endometrium in menstruating species: lessons learned from the animal kingdom†

Here we have summarized what is currently known about menstruating animal species with special emphasis on non-primate species: length of their menstrual cycle, ovulation, implantation, placentation, decidualization, and endometrial characteristics. Having an overview of all the possible animal models that can be used to study menstruation and the menstrual cycle could be useful to select the one that better matches the needs of the individual research projects. The most promising species to study menstruation seems to be the spiny mouse Acomys cahirinus. It is a rodent that could be easily held in the existing laboratory facilities for rats and mice but with the great advantage of having spontaneous menstruation and several human-like menstrual cycle characteristics. Among the species of menstruating bats, the black mastiff bat Molossus ater and wild fulvous fruit bat Rousettus leschenaultii are the ones presenting the most human-like characteristics. The elephant shrew seems to be the less suitable species among the ones analyzed. The induced mouse model of menstruation is also presented as an adaptable alternative to study menstruation.

A retrospective multicenter study of bone mineral density in adolescents and adults with Turner syndrome in Japan

Osteoporosis is one of the clinical features of women with Turner syndrome (TS). The reasons for low bone mineral density (BMD) and increased bone fragility are multifactorial, including estrogen deficiency, X-chromosome abnormalities, and environmental factors. Few, large-scale studies on bone mineral density in either adolescents or adults with TS have been done in Japan. The goal of the present study was to investigate spinal BMD in women with TS, assess its relationship with clinical parameters, especially estrogen replacement therapy, and investigate its longitudinal changes. The spinal BMD and clinical data of 149 Japanese women with TS aged 15 to 49 years who were followed at the four participating hospitals were retrospectively analyzed. The BMD Z-scores of the women with TS ranged from -5.30 to +1.89. Women with TS aged 15-39 years had lower BMD than healthy Japanese women (p < 0.01) while women with spontaneous menstruation had a significantly higher BMD Z-score than those without spontaneous menstruation (-0.73 ± 1.11 vs. -1.67 ± 1.18, p < 0.01). In women without spontaneous menstruation, BMD Z-scores correlated with the duration of their estrogen therapy (r = 0.167, p < 0.01). Women aged 15-39 years with TS had low BMD, which was associated with primary amenorrhea and short estrogen replacement therapy duration.

Comparison of traditional and step up protocols with letrozole

To compare time to ovulation between traditional and step up protocols with letrozole. Retrospective cohort. Patients were identified through Duke Fertility Center’s Intrauterine Insemination database, which stores information about each ovulation induction cycle including patient’s age, body mass index (BMI), last menstrual period, trigger date, and outcomes. The electronic medical record was used to obtain missing data points. Patients receiving ovulation induction with letrozole for ovulatory dysfunction between January 1, 2010 and March 3, 2018 were included. Patients were excluded if they received gonadotropins or if they switched to a different ovulation induction agent. In the traditional protocol, patients had an increase in letrozole dose following spontaneous menstruation or medroxyprogesterone-induced withdrawal bleed if there were no follicles at 16mm or greater on ultrasound by cycle day 20. Patients were excluded if they delayed starting a cycle with the increased dose. In the step up protocol, patients had an immediate increase in letrozole dose by cycle day 20 at the latest if no developing follicle was detected. A separate cohort of those who underwent a step up protocol with clomiphene was also included for comparison. The primary outcome was time to ovulation, defined as the number of days between the last menstrual period and the detection of a follicle at 16mm or greater on ultrasound. A secondary outcome was clinical pregnancy. Student’s t-test or Wilcoxon rank sum test were used to compare variables. Statistical analyses were conducted using R version 3.5.1 (Vienna, Austria). 49 patients were included: 21 in the traditional letrozole cohort, 15 in the step up letrozole cohort, and 13 in the step up clomiphene cohort. All cycles with traditional protocols occurred before January 2014 while step up protocols occurred after. The median age and IQR of patients in the traditional letrozole protocol cohort was 33 (31-35) vs. 28 (27-30) in the step up letrozole protocol, and the median BMI was 29 (25-36) vs. 34 (27-39). The time to ovulation was twice as long at 50.6 days for patients who underwent traditional letrozole protocol compared to the 21.9 days for those who underwent the step up letrozole protocol (p<0.0001). There was no difference in clinical pregnancy rate per cycle (10% [2/20] vs. 0% [0/14], p=0.16). In comparing letrozole step up cycles with clomiphene step up cycles, there was no difference in time to ovulation (21.9 vs. 21.1 days, p=0.47) or clinical pregnancy rate per cycle (0% [0/14] vs. 16.7% [2/12], p=0.17). No significant side effects were reported in any group. The step up letrozole protocol allows for faster time to ovulation in initially nonresponsive patients with ovulatory dysfunction. Similar to findings seen with clomiphene, it is not essential to have menstruation prior to increasing letrozole doses for ovulation induction.

Amenorrhea in adolescents: a narrative review

Background and Objective: Amenorrhea is the absence of spontaneous menstruation in women of reproductive age. Understanding the normal menstrual physiology and regulatory processes is important in differentiating etiologies when evaluating amenorrhea. In adolescents, amenorrhea may warrant investigation, and pregnancy should always be ruled out. In young female adolescents, amenorrhea can be the presenting symptom of different conditions such as polycystic ovary syndrome, eating disorders, or female athlete triad. It is particularly important that menstrual cycle disorders be appropriately analyzed due to potentially serious and detrimental consequences of amenorrhea. Early diagnosis is essential to yielding more favorable outcomes. If not addressed early, future negative implications may ensue. Methods: An electronic search was performed on MEDLINE and PubMed to identify relevant articles from 1990 to 2019. Key Content and Findings: This narrative review focuses on primary and secondary amenorrhea and the best practical approach in evaluating and managing affected adolescent females. Conclusions: Understanding normal menstrual physiology is crucial in recognizing concerns related to amenorrhea in adolescents. Prompt evaluation is necessary and diagnosis is warranted. Provision of appropriate care that is safe and evidence-based can prevent future negative health implications such as infertility and compromised bone health.

A Rare Case of Swyer Syndrome

Swyer syndrome is caused by abnormal sex differentiation during the embryonic period, resulting in incomplete intrauterine masculinization and undifferentiated gonads. The present case report describes a patient with Swyer syndrome associated with gonadoblastoma. At age of 16 years, this patient reported with primary amenorrhea at Gynae Department of the BIRDEM general Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect to axillary hair, breasts and pubic hair; she had normal vagina and a small cervix. As her examination findings revealed normal, she was referred to Endocrine outpatient (OPD) for further evaluation. Her karyotyping revealed 46XXY, abdominal ultrasonography revealed adnexal tumor in both sides. On laparotomy, complex tumor was found in both adnexal regions and both ovaries were resected and histopathology revealed gonadoblastoma. The patient was subjected to subsequent chemotherapy. She was treated with a combination of estrogens and progestogens to induce cyclical bleeding, which she discontinued after 3 years. She was lost to follow up for 16 years and again reported to endocrine OPD with irregular menstrual bleeding. Presence of any residual gonadal functional tissue was searched both biochemically and by imaging and the result was negative. Her menstruation was stopped by progestogens and which later on withdrawn successfully without any further onset of menstruation. In conclusion, this report describes an extremely rare case of Swyer syndrome with gonadoblastoma and spontaneous menstruation after a long period of discontinuation of hormone replacement treatment.&#x0D; Birdem Med J 2019; 9(2): 174-176

Ovarian function after allogeneic hematopoietic stem cell transplantation in children and young adults given 8‐Gy total body irradiation‐based reduced‐toxicity myeloablative conditioning

The spectrum of late sequelae after hematopoietic stem cell transplantation (HSCT) includes infertility, which is the most frequent complication. Some reports suggested that ovarian function may be better preserved in females undergoing HSCT with reduced-intensity conditioning (RIC) than with conventional myeloablative conditioning (MAC). However, the impact of HSCT after 8-Gy TBI-based reduced-toxicity MAC (RTMAC), whose efficacy is between those of conventional MAC and RIC, on ovarian function remains unclear. A single-center retrospective analysis of data derived from patient information for all the children who underwent transplantation at the Shinshu University Hospital was carried out. Patients who underwent 8-Gy total body irradiation (TBI)-based RTMAC before HSCT were analyzed. A total of 36% (five of 14) of the patients developed primary ovarian insufficiency (POI) during the observation period, but serum follicle-stimulating hormone levels reduced to normal range with spontaneous menstruation in two, implying the reversal of POI. Furthermore, only one (10%) of the 10 prepubertal patients (71%; 10/14) at the time of HSCT suffered from POI at the last observation, but all three post-pubertal patients developed POI (100%), and two (67%) continued to suffer from POI at the last observation. Taken together, 8-Gy TBI-based RTMAC before HSCT may decrease the possibility of POI compared with conventional MAC, especially in prepubertal patients. A longer follow-up will be required to ascertain whether a normal pregnancy and delivery can occur in such patients.