Resumption Of Menstrual Cycles Research Articles

P-605 Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA

Abstract Study question Is there a relationship between the biomechanical characteristics of ovarian cortex of POI patients and the resumption ovarian function after Drug-Free IVA? Summary answer Physical properties of ovarian cortex in POI are different. A significant ovarian stiffness increase was observed when resumption of ovarian function occurred after Drug-Free IVA. What is known already There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. Primordial follicles are localized at the collagen-rich ovarian cortex, which offers a rigid physical environment that supports follicular architecture and increases survival. Therefore, premature loss of ovarian function would be associated with a physically less rigid ovarian cortex. Study design, size, duration Prospective observational cohort study at a tertiary-care university hospital including POI patients according ESHRE criteria who underwent Drug-Free IVA by laparoscopy between January 2018 and December 2019 and were follow-up for a year after intervention. Participants/materials, setting, methods Nineteen patients were included. Resumption of ovarian function was defined as resumption of menstrual cycles (at least three consecutive episodes of menstrual bleeding) and/or the presence of follicles > 10 mm on ultrasound. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure mechanical properties at the nanometer scale (Young’s elastic modulus, E). Main results and the role of chance Median data at intervention were: age = 35 years (28–39); length of amenorrhea = 2 years (1–10); FSH level = 104.4 mIU/ml (38.9–176); and AMH = 0.02 ng/ml (0.01–0.1). Resumption of ovarian function was observed in 10 patients (52.6 %), achieving 2 pregnancies (one spontaneous and one after an IVF cycle). Median stiffness (E) measured by AFM was 2583 Pa (999–11296). There were no differences in clinical and hormonal parameters as a function of resumption of ovarian activity. Remarkably, ovarian cortex stiffness was significantly increased in patients with ovarian activity after Dug-Free VIA: 5519 (2260–11296] vs 1501 [999–3474], p value <0.001. Limitations, reasons for caution The main limitations of the study are the unavailability of ovarian tissue samples from a control group of patients without POI and the inability to perform histological studies on the same samples in which the biomechanical study was carried out. Wider implications of the findings These findings show the high variability of ovarian cortex stiffness in POI and that the increase of this stiffness entails a more favorable status after Drug-Free IVA. This may be related to an ovary with more residual follicles, which would explain a greater chances of ovarian follicular reactivations after treatment. Trial registration number not applicable

Resumption of menstrual cycles after 14 years of amenorrhea in a woman infected with Mycobacterium africanum

The most common site of tuberculosis is the lung. However, it can also affect the fallopian tubes or endometrium. We report a woman with a narrow and tubular uterine cavity due to Mycobacterium africanum. The endometrium was fibrotic leading to amenorrhea of over a decade. Despite treatment with multiple anti-tuberculosis medication and hysteroscopic adhesiolysis, menstrual cycles resumed only a few years later. It shows that the endometrium regenerates overtime.

Ligating Internal Iliac Artery: Success beyond Hesitation.

To study the outcomes, benefits and complications of internal iliac artery ligation in both obstetric and gynecological cases. To study the outcomes, effectiveness and complications of internal iliac artery ligation (IIAL). This is an analytical longitudinal study done among women who have undergone internal iliac artery ligation in Dr. BRAMH a tertiary referral center from July 2013 to June 2015. Follow-up was done through color Doppler analysis of pelvic arteries before discharge, after 6weeks and after 6months. The efficacy of IIAL was 96.87%. The mean shock index was 0.94±0.26. Sixty-four women underwent IIAL out of which placenta previa (21.8%) was the major indication. There were four maternal deaths. There were no intraoperative or ischemic complications. The greater the time interval between onset of hemorrhage and IIAL, the graver the outcome. For all women in whom uterus could be salvaged, resumption of menstrual cycles was seen within 6months of IIAL. There was a significant decrease in the RI and PI of uterine arteries. In the ovarian arteries, there was a significant increase in RI and no significant change in PI initially. Flow in distal part of ligated internal iliac arteries could be detected in 54 (90%) women out of 60 after 6months of ligation of internal iliac arteries. IIAL is an effective life-saving method to control obstetric and gynecological hemorrhage, and a hysterectomy can often be avoided. Early resort to IIAL is vital for improving the patient outcome. Uterine perfusion is well maintained, while there may be a decrease in ovarian perfusion. Resumption of menstrual cycles and presence of distal flow in internal iliac artery within 6months suggest the preservation of future fertility; in order to better understand the impact of IIAL on ovarian functions and future fertility, larger studies with longer follow-up periods need to be conducted.

The effect of short-term stress on serotonin gene expression in high and low resilient macaques.

Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. When stressed with a paradigm of relocation and diet for 60 days, or 2 menstrual cycles, highly stress resilient monkeys continue to ovulate during both stress cycles (HSR); medium stress resilient monkeys ovulate once (MSR) and stress sensitive monkeys do not ovulate for the entire 60 days (SS). This study examines serotonin-related gene expression in monkeys with different sensitivity to stress and exposed to 5 days of moderate stress. Monkeys were first characterized as HSR, MSR or SS. After resumption of menstrual cycles, each monkey was re-stressed for 5 days in the early follicular phase. The expression of 3 genes pivotal to serotonin neural function was assessed in the 3 groups of monkeys (n=4-5/group). Tryptophan hydroxylase 2 (TPH2), the serotonin reuptake transporter (SERT), and the 5HT1A autoreceptor mRNAs expression were determined at 4 morphological levels of the dorsal raphe nucleus with in situ hybridization (ISH) using digoxigenin-incorporated riboprobes. In addition, cFos was examined with immunohistochemistry. Positive pixel area and/or cell number were measured. All data were analyzed with ANOVA (3 groups) and with a t-test (2 groups). After 5 days of stress, TPH2, SERT, 5HT1A and cFos were significantly lower in the SS group than the HSR group (p<0.05, all). This pattern of expression was the same as the pattern observed in the absence of stress in previous studies. Therefore, the ratio of the HSR/SS expression of each serotonergic gene was calculated in the presence and absence of stress. There was little or no difference in the ratio of HSR/SS gene expression in the presence or absence of stress. Moreover, cFos expression indicates that overall, cell activation in the dorsal raphe nucleus and periaquaductal gray is lower in SS than HSR animals. These data suggest that the serotonin system may set the sensitivity or resilience of the individual, but serotonin-related gene expression may not rapidly respond to moderate stress in nonhuman primates.

Preliminary results of the first human uterus transplantation from a multiorgan donor

To describe the first-year results of the first human uterus transplantation case from a multiorgan donor. Case study. University hospital. A 21-year-old woman with complete müllerian agenesis who had been previously operated on for vaginal reconstruction. Uterus transplantation procedure consisting of orthotopic replacement and fixation of the retrieved uterus, revascularization, end to site anastomoses of bilateral hypogastric arteries and veins to bilateral external iliac arteries and veins was performed. Resumption of menstrual cycles. The patient had menarche 20 days after transplant surgery. She has had 12 menstrual cycles since the operation. We have described the longest-lived transplanted human uterus to date with acquirement of menstrual cycles.

Ovarian Preservation by GnRH Agonists during Chemotherapy: A Meta-Analysis

Treatment with cyclophosphamide (CYC) confers up to a 40% risk of ovarian failure in women of reproductive age. The use of GnRH agonists (GnRHa) to preserve ovarian function has been investigated in several small studies. We performed a systematic review of studies examining whether a GnRHa administered during chemotherapy is protective of ovarian function and fertility. We searched the English-language literature (1966-April 2007) using MEDLINE and meeting abstracts and included studies that reported an association between GnRHa and ovarian preservation in women receiving chemotherapy. Studies without a control group were excluded. Ovarian preservation was defined as the resumption of menstrual cycles and a premenopausal follicle-stimulating hormone (FSH) after chemotherapy. Fertility was determined by a woman's ability to become pregnant. We estimated the summary relative risk (RR) and associated 95% confidence intervals (95% CI) using a random-effects model. Nine studies included 366 women. Three studies included women with autoimmune disease receiving CYC; six included women with hematologic malignancy receiving combination chemotherapy. In total, 178 women were treated with GnRHa during chemotherapy, 93% of whom maintained ovarian function. Of the 188 women not treated with GnRHa, 48% maintained ovarian function. The use of a GnRHa during chemotherapy was associated with a 68% increase in the rate of preserved ovarian function compared with women not receiving a GnRHa (summary RR = 1.68, 95% CI 1.34-2.1). Among the GnRHa-treated women, 22% achieved pregnancy following treatment compared with 14% of women without GnRHa therapy (summary RR = 1.65, CI 1.03-2.6). Based on the available studies, GnRHa appear to improve ovarian function and the ability to achieve pregnancy following chemotherapy. Several randomized trials are underway to define the role and mechanism of GnRHa in ovarian function preservation. In the meantime, premenopausal women facing chemotherapy should be counseled about ovarian preservation options, including the use of GnRHa therapy.

Comparison of metabolic effects of metformin and rosiglitazone in the management of polycystic ovary syndrome (PCOS): A prospective, parallel, randomized, open-label study

Summary Background and aims Effective treatment of polycystic ovary syndrome (PCOS) remains controversial but recently, insulin-sensitizing agents have found usage in PCOS based on the relationship between hyperinsulinemia and ovarian hyperandrogenemia. The present study was undertaken to evaluate and compare the efficacy of metformin versus rosiglitazone on insulin resistance and hyperandrogenemia in women with PCOS. Methods In this prospective, parallel, randomized, open-label study; insulin resistance and hyperandrogenemia were evaluated in 61 subjects with PCOS, out of which 31 subjects received metformin (850 mg/BD) and 30 subjects received rosiglitazone (2 mg/BD) for 12 months. Evaluation of insulin resistance using the homeostasis model insulin resistance index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), area under the curve (AUC) for insulin and AUC for glucose; and evaluation of hyperandrogenemia by clinical/biochemical parameters namely, hirsutism, ovulation, resumption of menstrual cycle, and androgen levels were performed at baseline and 3,6 and 12 months, respectively. Results Clinical manifestations of hyperandrogenemia improved in both groups. Both PCOS groups had normal levels of glucose throughout the study. Insulin levels, at baseline and months 3, 6 and 12 were 13.11 ± 2.45, 9.94 ± 2.41, 9.28 ± 3.25, 8.94 ± 2.39 and 11.38 ± 5.16, 9.55 ± 3.11, 8.22 ± 3.68, 8.02 ± 3.78 μU/ml in metformin and rosiglitazone groups respectively (P Conclusion Metformin and rosiglitazone improve outcome measures after treatment; rosiglitazone seems to improve insulin resistance relatively earlier; while metformin had an earlier and more sustained benefit on hyperandrogenemia.

Relation of supplementary feeding to resumptions of menstruation and ovulation in lactating postpartum women

Resumption of menstrual cycles is one of the indicators for restoration of reproductive capability in postpartum women. However, menstruation does not necessarily mean that ovulation has taken place. The aim of this study was to investigate the relation of supplementary feeding to return of menstruation and ovulation after delivery. A questionnaire was used to obtain data from 101 breastfeeding mothers. The following elements were analyzed: age, education level, breastfeeding practice, time of return of menstruation, contraceptive practice, and starting time of supplementary feeding during the lactation at intervals of 6 weeks to 18 months after delivery. The ovulation was continuously monitored by ultrasonography and basal body temperature (BBT) measurement. By ultrasonography, 53 of the 101 women (52.5%) had the first ovulation (follicle > 1.8 cm in diameter) within 154 days after delivery on average, among whom 11 (10.9%, 11/101) had restoration of ovulation within 4 months and 42 (41.6%, 42/101) had it after 4 months. In women with follicles > 1.8 cm in diameter (n = 53), the menstruation resumed (138 +/- 84) days after delivery, and the supplementary feeding was started at (4.0 +/- 1.1) months, which were significantly earlier than those in the women with follicular diameter < 1.7 cm (n = 48; (293 +/- 88) days, (5.1 +/- 1.3) months; t = 9.003, P < 0.01 and t = 4.566, P < 0.01). In the women with follicles < 1.8 cm in diameter, 30 had return of menstruation before the end of ultrasonographic monitoring, while only 8 in the women with follicular diameter < 1.7 cm had menstrual resumption at the same time (chi(2) = 16.91, P < 0.01). The starting time of supplementary feeding was positively correlated with the time of the restoration of menstruation (n = 100, r = 0.4764, P < 0.01) and first ovulation after delivery (n = 53, r = 0.5554, P < 0.01). In this series, no woman had pregnancy within 18 months postpartum. Supplementary feeding can affect the restoration of menstrual cycles and ovulation in lactating postpartum women.

Retentissement osseux de l’anorexie mentale

The objective of this study was to evaluate the epidemiology, diagnosis, pathophysiology, and treatment of bone loss related to anorexia nervosa. Earlier onset and longer duration of anorexia nervosa are associated with more severe bone loss. Osteoporosis develops in 38 to 50% of cases. Bone mineral density measurement by dual-energy X-ray absorptiometry is useful for assessing bone mass, and bone marker assays provide information on bone turnover. Bone loss in anorexia nervosa is probably multifactoriel. Estrogen deficiency was long felt to be the major factor. However, in contrast to postmenopausal osteoporosis, bone loss associated with anorexia nervosa is related mainly to inadequate bone formation, with only a slight increase in bone resorption. This suggests a role for nutritional factors, such as disturbances in the growth hormone-somatomedin C axis (GH/IGF-I) related to malnutrition. The best treatment strategy for correcting bone mass in patients with anorexia nervosa is not agreed on. Resumption of menstrual cycles and weight gain seem necessary but not always sufficient. Studies found no benefits with estrogen therapy, but this was usually given as estrogen–progestin contraceptives. No vast studies evaluating hormone replacement therapy have been reported. Bone formation enhancers such as IGF-I seem to provide the best results, most notably when used in combination with estrogens. This suggests that complex treatment strategies combining bone formation enhancers and bone resorption inhibitors may deserve evaluation.

Bone loss associated with anorexia nervosa

The objective of this study was to evaluate the epidemiology, diagnosis, pathophysiology, and treatment of bone loss related to anorexia nervosa. Earlier onset and longer duration of anorexia nervosa are associated with more severe bone loss. Osteoporosis develops in 38–50% of cases. Bone mineral density measurement by dual-energy X-ray absorptiometry is useful for assessing bone mass, and bone marker assays provide information on bone turnover. Bone loss in anorexia nervosa is probably multifactorial. Estrogen deficiency was long felt to be the major factor. However, in contrast to postmenopausal osteoporosis, bone loss associated with anorexia nervosa is related mainly to inadequate bone formation, with only a slight increase in bone resorption. This suggests a role for nutritional factors, such as disturbances in the growth hormone–somatomedin C axis (GH/IGF-I) related to malnutrition. The best treatment strategy for correcting bone mass in patients with anorexia nervosa is not agreed on. Resumption of menstrual cycles and weight gain seem necessary but not always sufficient. Studies found no benefits with estrogen therapy, but this was usually given as estrogen–progestin contraceptives. No vast studies evaluating hormone replacement therapy have been reported. Bone formation enhancers such as IGF-I seem to provide the best results, most notably when used in combination with estrogens. This suggests that complex treatment strategies combining bone formation enhancers and bone resorption inhibitors may deserve evaluation.

Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity.

Anorexia nervosa (AN) is associated with very low levels of leptin, a cytokine secreted by adipose tissue and known to suppress appetite. Leptin may play a permissive role in onset of puberty and in resumption of gonadal function in conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure of the free leptin index (FLI), which may be a more accurate determinant of leptin function. Determinants of sOB-R and FLI have not been examined in an adolescent population. We examined levels of sOB-R, leptin, and FLI, and body composition and hormonal determinants of these variables in 23 adolescent girls with AN and 21 healthy adolescent girls of comparable maturity prospectively over 1 yr. Measures of insulin resistance and adiponectin were also examined. We determined changes in levels of sOB-R, leptin, and FLI with weight recovery (defined as an increase in body mass index of >/=10%, n = 11), and with resumption of menstrual cycles (n = 13). Girls with AN had significantly higher levels of sOB-R (P = 0.0008) and significantly lower levels of leptin and FLI (P < 0.0001 for both) than healthy controls, and levels of FLI were reduced more than levels of leptin in girls with AN compared with controls. An inverse correlation was noted between levels of leptin and sOB-R for the group as a whole (r = -0.64, P < 0.0001) but not in girls with AN considered alone. The most important predictor of levels of sOB-R was cortisol in the group as a whole (r = 0.61, P < 0.0001) and in girls with AN considered alone (r = 0.66, P = 0.0008). Other independent predictors of sOB-R levels for the entire group were percent body fat (r = -0.44, P = 0.003) and levels of IGF-I (r = -0.37, P = 0.01). The most important predictors of leptin and FLI were body mass index and percent body fat. An inverse relationship was noted between measures of insulin resistance and sOB-R levels, whereas a positive association was noted between these measures and leptin and FLI. Adiponectin values did not differ in girls with AN compared with healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight recovery resulted in significant decreases in levels of the sOB-R (24.7 +/- 1.7 to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0 to 13.7 +/- 2.9 microg/liter, P = 0.02). Resumption of menstrual function, but not weight recovery alone, was associated with significant increases in FLI (0.19 +/- 0.04 to 0.50 +/- 0.09 microg/U x 10(-3), P = 0.02).We demonstrate an increase in levels of sOB-R and a decrease in the FLI in adolescent girls with AN, and also demonstrate that cortisol is the most important predictor of levels of sOB-R in this condition. Levels of leptin and FLI, conversely, are primarily predicted by body composition. Weight recovery is associated with a decrease in sOB-R and an increase in leptin. Resumption of menses is associated with significant increases in the FLI, suggesting that free leptin may be an important determinant of menstrual recovery.

Lactational Amenorrhea

There is no doubt that suckling can cause a substantial delay in the resumption of fertility postpartum in all societies regardless of nutritional status. The variability in duration of infertility is directly related to the different patterns of suckling, an uncontrollable variable specific to the mother and child. Resumption of fertility proceeds in two parts, an initial phase of amenorrhea in which ovarian follicle growth is suppressed or attenuated followed by a resumption of menstrual cycles often associated with inadequate luteal function contributing to the reduced fertility of lactating menstruating women. Suckling appears to suppress the normal pattern of pulsatile release of GnRH and hence LH and prevents the normal growth of follicles. The normal positive feedback effect of estrogen on LH release is abolished, and estradiol exerts an enhanced negative feedback effect on both LH and FSH. Thus, while suckling continues, any follicle that starts to develop and secrete estradiol will inhibit further LH release and therefore stop growing. When suckling declines, the pulsatile pattern of LH returns to normal, sensitivity to estrogen negative feedback declines, and follicle growth can continue and ovulation will occur. Opiates do not appear to be mediators of the suckling-induced suppression of GnRH or the release of prolactin in women. There is no clear role for prolactin per se or nutritional status in the suppression of ovarian activity postpartum. Thus, while the suppression of fertility in breast-feeding women plays an extremely important role in limiting populations, the mechanism whereby the suckling stimulus from the nipple causes the disruption in GnRH release from the hypothalamus remains to be elucidated.

Treatment of macroprolactinomas with the long-acting and repeatable form of bromocriptine: a report on 29 cases.

Twenty-nine patients with macroprolactinomas were treated by monthly intramuscular injections of the long-acting and repeatable form of bromocriptine (Parlodel-LAR) in doses ranging from 50-150 mg. They were divided into two groups: group I consisted of 22 patients who received Parlodel LAR before transsphenoidal adenomectomy; group II was composed of 7 patients with earlier neurosurgery and of 2 patients from group I not cured by transsphenoidal adenomectomy. Duration of therapy varied from 1-12 months, and a total of 104 injections was given. At nadir day, serum PRL levels were situated between less than 1% and 43% of pretreatment values. At day 28 after the first injection, serum PRL levels varied between less than 1% to 139% of initial values. No difference could be detected between the two groups regarding the percent of PRL inhibition. Long-term treatment with Parlodel-LAR resulted in a sustained inhibition of PRL secretion, except for 1 case. Resumption of menstrual cycles occurred in 4 out of 15 women and correction of hypogonadism in 4 out of 14 men. Amelioration of disturbed visual fields was recorded in 3 out of 8 patients. Diminution of the adenoma volume was radiologically documented in 14 out of 22 cases. Only few and mild side effects were recorded. One patient with partial adrenal deficiency suffered from a syncope, but this was prevented by hydrocortisone supplementation during the subsequent Parlodel-LAR administration. In conclusion, Parlodel-LAR proved effective in the treatment of macroprolactinomas, achieving rapid inhibition of PRL secretion, and in some patients amelioration of hypopituitarism, reduction in tumor size, and improvement in visual fields, and caused no serious side effects. It is a valuable preparation to surgery and can also be used in long-term medical therapy.

Body fat, puberty and fertility.

Summary1. The high percentage of fat, about 26–28% in the mature human female, may influence reproductive ability directly through two mechanisms: (a) fat converts androgens to oestrogens; (b) relative fatness influences the direction of metabolism of oestrogen to the most potent or least potent forms. The relative degree of fatness thus is directly related to both the quantity of circulating oestrogen and the biological effectiveness of the oestrogen. This is a neat mechanism for relating rates of growth, nutrition and energy outputs to the energy requirements for reproduction. Fat is the most labile body tissue; it therefore reflects environmental changes more rapidly than other tissues of the body.2. The slow maturation of the hypothalamus and pituitary up to menarche, or first oestrus, is accompanied by a slow maturation of the body, which changes not only in size but in the relative proportion of bone, muscle, and fat. Evidence is presented that a particular threshold ratio of fat to lean mass is normally necessary for puberty and the maintenance of female reproductive ability in the human and in the rat. The synchronizing mechanisms may be metabolic, relating food intake to core temperature and/or fat storage.3. Undernutrition and weight loss in the range of 10–15 % of normal weight for height delays menarche and causes amenorrhoea. Ballet dancers and athletes also have delayed menarche and amenorrhoea. The cessation of reproduction in both groups can be considered adaptive. Refeeding and/or cessation of intense activity results in the initiation or resumption of menstrual cycles after varying periods of time. A necessary threshold weight for height can be predicted from a fatness index.4. Differences in the natural fertility of historical and contemporary populations may be explained by a direct effect of food intake and energy outputs on fecundity.5. The late maturing fat ‐ ‘sex fat’ ‐ may have a special role in reproduction.