Kuntai Capsule Combined With Letrozole on Gonadal Hormone Levels and Ovarian Function in Patients With PCOS: A Systematic Review and Meta-Analysis.

Background: The efficacy of Kuntai capsule combined with letrozole (LE) in improving ovarian function of polycystic ovary syndrome (PCOS) has been evaluated before, but there is still a lack of evidence-based support for the regulation of sex hormone levels. In recent years, new randomized clinical trials (RCTs) have been reported on the effect of combined therapy on regulating sex hormone levels. Objective: We aimed to systematically evaluate the efficacy of Kuntai capsule combined with LE in the treatment of PCOS. Methods: A search across the China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang database, PubMed, Web of Science, The Cochrane Library, and Embase was conducted on Kuntai capsule combined with LE in the treatment of PCOS. The time of the self-built database was up to April 30, 2021. RCTs of LE in the control group and LE combined with Kuntai capsule in the experimental group were selected. RevMan5.3 software was used for data analysis. Results: A total of 17 studies were gathered, which included 1,684 patients. The meta-analysis results showed that the total effective rate of the combined group was 93.36% and that of the LE group was 78.15%. The improvement in the ovulation rate, pregnancy rate, number of mature follicles, endometrial thickness, cervical mucus score, and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) in the combined group was consistent with the results of a previous meta-analysis and was better than that in the LE group (p < 0.05). In addition, the combination group was better than the LE group in regulating the levels of estradiol (E2) and testosterone (T) (p < 0.05). There were no adverse drug reactions in the two groups during treatment. Conclusion: As a type of pure traditional Chinese medicine preparation, Kuntai capsule combined with LE had a better effect than LE alone in the treatment of PCOS, with advantages mainly reflected in enhancing ovarian function and regulating the levels of sex hormones in vivo, among others, but the value of combined therapy still needs to be verified by more high-quality RCTs.

Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer.

RESEARCH QUESTION: An important discussion point before chemotherapy is ovarian toxicity, a side-effect that profoundly affects young women with cancer. Their quality of life after successful treatment, including the ability to conceive, is a major concern. We asked whether serum anti-Müllerian hormone (AMH) measurements before chemotherapy for two most common malignancies are predictive of long-term changes in ovarian reserve? DESIGN: A prospective cohort study measured serum AMH in 66 young women with lymphoma and breast cancer, before and at 1 year and 5 years after chemotherapy, compared with 124 healthy volunteers of the same age range (18-43 years). Contemporaneously, patients reported their menses and live births during 5-year follow-up. RESULTS: After adjustment for age, serum AMH was 1.4 times higher (95% CI 1.1 to 1.9; P < 0.02) in healthy volunteers than in cancer patients before chemotherapy. A strong correlation was observed between baseline and 5-year AMH in the breast cancer group (P < 0.001, regression coefficient = 0.58, 95% CI 0.29 to 0.89). No significant association was found between presence of menses at 5 years and serum AMH at baseline (likelihood ratio test from logistics regression analysis). CONCLUSIONS: Reproductive-age women with malignancy have lower serum AMH than healthy controls even before starting chemotherapy. Pre-chemotherapy AMH was significantly associated with long-term ovarian function in women with breast cancer. At key time points, AMH measurements could be used as a reproductive health advisory tool for young women with cancer. Our results highlight the unsuitability of return of menstruation as a clinical indicator of ovarian reserve after chemotherapy.

Ovarian function after ovarian transposition and additional pelvic radiotherapy: A systematic review.

OBJECTIVE: To investigate the ovarian survival (OS) after ovarian transposition (OT) and pelvic radiation. DESIGN: Systematic review. Electronic databases were searched to identify studies on OT prior to external beam radiation therapy (EBRT, to the pelvic). Primary outcome was the ovarian function after radiotherapy and ovarian transposition. Secondary outcomes were complication-rate. Only studies in English, German or French were included. SETTING: Not applicable. PATIENTS: Fertile women undergoing ovarian transposition prior to pelvic radiation therapy. INTERVENTIONS: We included all studies, containing >5 patients, treated with OT prior to radiation therapy. MAIN OUTCOME MEASURE: Ovarian function. RESULTS: Our search yielded a total of 1130 studies of which 38 were eligible with a total of 765 patients. All studies were cohort studies or case-series. Heterogeneity among studies could not be rejected hence meta-analysis could not be performed. OS after OT and EBRT ranged from 20% to 100%. The median follow-up ranged from 7 to 102 months. OS was higher after OT and brachytherapy (OS 63.6-100%) when compared to OT and EBRT (20-100%) and OT concomitant chemoradiotherapy (0-69.2%). Only 22 studies (with 112 patients) reported on complications: among these studies the complication-rate was 0%-28.6%. CONCLUSION: From our systematic review of literature we conclude that the preservation of ovarian function after OT prior to EBRT is successful in 20-100% of patients. Most favorable outcome with regard to preservation of ovarian function is seen in patients after OT and BT, followed by OT and EBRT and OT and RT combined with chemotherapy.

Caracterización clínico-epidemiológica de parejas infértiles / Clinical-Epidemiological characterization of infertile couples

Introducción: Aproximadamente, el 15 por ciento de todos los matrimonios no tienen hijos. Según estudios realizados en Cuba, la prevalencia de infertilidad oscila entre 12 y 14 por ciento, destacándose dentro de sus causas los factores pélvicos que afectan las trompas o el endometrio con 30-50 por ciento, seguido de la disfunción ovulatoria con el 10 a 25 por ciento y solo 10 por ciento son de causa desconocida. Objetivo: Caracterizar a las parejas infértiles según variables clínico epidemiológicas seleccionadas. Métodos: Se realizó un estudio observacional, descriptivo, transversal a 224 parejas infértiles, en la provincia Santiago de Cuba. Cuba, en el periodo 2015-2016. Resultados: El 40,3 por ciento de las parejas estudiados presentaron infecciones de transmisión sexual de diferentes etiologías y el 45,6 por ciento se diagnosticaron con infertilidad secundaria. Conclusiones: La edad de la mujer por encima de los 35 años, los antecedentes patológicos personales, la ingestión de medicamentos, la presencia previa de infección de trasmisión sexual así como el antecedente de varios episodios de enfermedad pélvica inflamatoria, están relacionadas con la etiología infecciosa de la infertilidad y pudieran constituir las principales causas de este trastorno en nuestro país(AU)

Introduction: Approximately 15 percent of all marriages do not have any children. According to studies carried out in Cuba, the prevalence of infertility ranges from 12 to 14 percent, among whose highlighted causes are pelvic factors that affect the tubes or the endometrium, accounting for 30-50 percent, followed by ovulatory dysfunction, accounting for 10-25 percent, while only 10 percent are of unknown cause. Objective: To characterize infertile couples based in the selected clinical-epidemiological variables. Methods: An observational, descriptive, cross-sectional study was carried out with 224 infertile couples in Santiago de Cuba Province, Cuba, in the period from 2015 to 2016. Results: 40.3 percent of the studied couples had sexually transmitted infections of different etiologies, while 45.6 percent were diagnosed with secondary infertility. Conclusions: The age of the woman over 35 years, personal pathological antecedents, ingestion of medications, the previous presence of sexually transmitted infections, as well as the history of several episodes of pelvic inflammatory disease, are related to the infectious etiology of infertility and could be the main causes of this disorder in our country(AU)

Prediction of ovarian function recovery in young breast cancer patients after protection with gonadotropin-releasing hormone agonist during chemotherapy.

PURPOSE: This study evaluated predictive factors for recovery of ovarian function after ovarian protection by GnRH agonist during chemotherapy in young breast cancer patients. METHODS: This prospective cohort study analyzed 105 young breast cancer patients who were studied longitudinally after receiving GnRH agonist during cyclophosphamide-based chemotherapy for ovarian protection. Associations between pretreatment hormones, clinical factors, and recovery of ovarian function (resumption of menstruation or anti-Müllerian hormone (AMH) ≥ 1 ng/ml) were evaluated at 12 months and long-term follow-up after completion of chemotherapy. RESULTS: Mean age was 32 years (range 23-42 years). In multivariate analyses, tamoxifen use (P = 0.035) and pretreatment follicle-stimulating hormone (FSH) (P = 0.032) were predictive of resumption of menstruation, and age (P = 0.019), tamoxifen use (P = 0.022), pretreatment FSH (P < 0.001), and AMH (P = 0.040) were predictors for AMH ≥ 1 ng/ml at 12 months. In addition, pretreatment AMH was a predictor for AMH ≥ 1 ng/ml after long-term follow-up. Receiver operating characteristic curve analyses gave area under the curve of 0.805 for resumption of menstruation and 0.903 for serum AMH concentration ≥ 1 ng/ml at 12 months, when age, tamoxifen use, pretreatment FSH, and AMH were combined. CONCLUSION: Pretreatment AMH (3.26 ng/ml), age (33.9 years), pretreatment FSH (5.5 IU/l), and tamoxifen use are useful predictors for AMH ≥ 1 ng/ml at 12 months after GnRH agonist. This finding will support patient and clinician decision-making regarding fertility preservation.

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome.

OBJECTIVE: To compare androgen responses during ACTH infusion among women with polycystic ovary syndrome (PCOS) and healthy women. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Women with PCOS (n = 13) and healthy controls (n = 15). INTERVENTION(S): Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. MAIN OUTCOME MEASURE(S): Comparison of basal and stimulated levels of 17α-hydroxyprogesterone (17-OHP), androgens, and cortisol (F) during ACTH infusion with those after hCG injection within individual subjects. RESULT(S): In women with PCOS increased 17-OHP, androstenedione (A), and DHEA responses during ACTH infusion were comparable to those observed in healthy controls. The magnitude of responses was highly variable among women with PCOS. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in women with PCOS and healthy controls. CONCLUSION(S): Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. CLINICAL TRIAL REGISTRATION NUMBER: NCT00747617.

Ovarian reserve markers and assisted reproductive technique (ART) outcomes in women with advanced endometriosis.

BACKGROUND: The role of ovarian reserve markers as predictors of the controlled ovarian stimulation (COS) response in intracytoplasmic sperm injection (ICSI) cycles in women with endometriosis has been much debated. The aim of the present study is to assess the predictability of ovarian reserve markers for the number of mature oocytes (MII) retrieved and to assess the pregnancy rate and live birth rate in women with advanced endometriosis. METHODS: Two hundred eighty-five infertile women who had laparoscopy followed by a first ICSI cycle were recruited in this prospective study. One hundred ten patients were diagnosed with endometriosis stage III-IV (group 1), and 175 patients had no endometriosis (group II). Sixty-three patients in group 1 had no history of previous endometrioma surgery (group Ia), and 47 patients had a history of previous endometrioma surgery (group Ib). RESULTS: The number of mature oocytes retrieved was significantly lower in women with advanced endometriosis than in women with no endometriosis. The number of mature oocytes retrieved in women with and without endometriosis was best predicted by antral follicle count (AFC) and age, whereas only AFC was a predictor in women with previous endometrioma surgery (odds ratio: 0.49; 95% confidence interval: 0.13-0.60). Women with endometriosis had a lower rate of live births than the control group, but this difference was not statistically significant; the number of live births was significantly lower in those with previous endometrioma surgery. CONCLUSIONS: The best predictor of the COS response in ICSI was AFC, followed by age. Women receiving ICSI following surgery for ovarian endometrioma had a poorer clinical outcome and lower rate of live births compared with those with endometriosis but no previous surgery and the control group.

A highly-sensitive anti-Müllerian hormone assay improves analysis of ovarian function following chemotherapy for early breast cancer.

AIM: Anti-Müllerian hormone (AMH) shows promise as a biomarker of the ovarian reserve but current assays are insufficiently sensitive to allow assessment of this post-chemotherapy in most women. We have assessed a new highly sensitive AMH assay (Ansh picoAMH) in the evaluation of ovarian activity in women with very low ovarian reserve after chemotherapy. METHODS: A prospective cohort and an independent validation cohort of premenopausal women with early breast cancer (eBC) were recruited at the time of diagnosis (combined n=98), and ovarian reserve markers 2-5 years later following chemotherapy were assessed in relation to menstrual activity. RESULTS: The picoAMH assay had a limit of detection of 7.5 pg/ml. AMH clearly distinguished women with ongoing menses from those with amenorrhoea at 2 years after diagnosis (mean 522 ± 169 versus 8.9 ± 1.3 pg/ml, P<0.0001) with high predictive value for continuing menses or amenorrhoea for the subsequent 3 years. AMH was detectable in more women than using a previous assay (P=0.004). Other markers of the ovarian reserve (follicle-stimulating hormone (FSH), inhibin B) were also of discriminatory value but to lesser extents. This finding was validated in a second, independent cohort of women treated for eBC. CONCLUSION: The 10-fold increased assay sensitivity showed very clear distinction between groups based on ovarian activity with excellent prediction of future menses or amenorrhoea. This will improve assessment of post-chemotherapy ovarian function in women and may aid treatment decisions.

The role of serum anti-Müllerian hormone (AMH) in the hormonal diagnosis of polycystic ovary syndrome.

BACKGROUND: The study was performed to validate the threshold for anti-Müllerian hormone (AMH) that suggests the presence of polycystic ovaries in women with polycystic ovary syndrome (PCOS). METHODS: This prospective observational study included 59 infertile women: (A) 22 PCOS with hyperandrogenism (HA) and oligo-anovulation, (B) 15 suspected PCOS with either HA or oligo-anovulation and (C) 22 asymptomatic control women. The diagnosis of PCOS was made according to the NIH classification. RESULTS: For serum AMH and follicle number, respectively, the areas under the receiver operating characteristic curve (A versus C) were 0.97 and 0.93. The best compromise between specificity (95% and 91%) and sensitivity (95% and 82%) was obtained with threshold values of 33 pmol/l and 13 follicles, respectively. Using a serum AMH > 33 pmol/l as a surrogate for either HA or oligo-anovulation in group B would lead to the diagnosis of PCOS in seven (46.6%) patients from this group. CONCLUSIONS: Our data confirms that the AMH assay has a high diagnostic potential, providing that an appropriate threshold is used. AMH measurement may be included as an ultimate diagnostic criterion for the diagnosis of PCOS when either HA or anovulation is missing and/or when no reliable antral follicle count can be obtained.

Dynamic tests of ovarian reserve: a systematic review of diagnostic accuracy.

Despite a plethora of tests of ovarian reserve, there is no perfect test to predict pregnancy. Recent evidence points that anti-Müllerian hormone and antral follicle count may be better than other tests, although other tests continue to be used and form the basis of exclusion of women from fertility treatments. This systematic review concentrated on dynamic tests of ovarian reserve [clomifene citrate challenge test (CCCT), gonadotrophin-releasing hormone agonist stimulation test (GAST) and exogenous FSH ovarian reserve test (EFORT)] and assessed their predictability in terms of fertility outcomes. The study did not restrict itself to women undergoing IVF. The diagnostic odds of abnormal CCCT for non-pregnancy were 2.11 (95% confidence interval, 1.04-4.29) at FSH >10 IU/l (day 3 or 10). The diagnostic accuracy of GAST and EFORT could not be determined due to inconsistencies in the way these tests were conducted. This systematic review and meta-analysis was limited by heterogeneity in terms of the population sampled and the index and reference tests. There is an urgent need for consensus on the performance of these tests and the definition of normality, if their use is to be continued. However, given the present level of evidence, these tests should be completely abandoned.

Ovarian reserve evaluation: state of the art.

PURPOSE: Revise role of hormonal basal and dynamic tests, as well as ultrasonographic measures as ovarian reserve markers, in order to provide better counseling to subfertile couples. METHODS: Review of publications on the topic, with an emphasis on recent well designed articles. RESULTS: Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, even for premature ovarian senescence patients who do not present subfertility complaints. However, these markers occupy important place in initial approach to treatment of subfertile couples, predicting unsatisfactory results that could be improved by differentiated induction schemes and reducing excessive psychological and financial burdens, and adverse effects. CONCLUSIONS: In order to remedy the limitations due to the scarcity of strong evidence about this topic, future studies should try to clarify predictive value of markers in groups of specific diseases-related subfertility and pay special attention to propaedeutic multivariate models including anti-Müllerian hormone and antral follicle count.

Clomiphene citrate challenge test and serum anti-Müllerian hormone levels in women with menstrual irregularities and/or infertility.

AIM: Evaluation of CCCT results and anti-Müllerian hormone (AMH) plasma levels in women with menstrual cycle irregularities and/or infertility. PATIENTS AND METHODS: 70 patients with menstrual cycle disturbances were recruited to the study. Clomiphene citrate challenge test (CCCT) was carried out in each patient enrolled. At day 3 of the cycle plasma basic levels of FSH, estradiol, progesterone, IGFBP-1, TSH, prolactin, DHEAS and anti-Müllerian hormone were measured. At day 10 of the cycle plasma levels of FSH and estradiol were evaluated. Plasma levels of hormones were measured by commercially available ELISA kits. RESULTS: 50 women with normal result of CCCT (group A) had higher mean plasma level of AMH compared to 20 women with abnormal result of CCCT (group B). Mean plasma FSH level at day 3 of the cycle was lower in group A compared to group B. There were no other statistically significant differences in mean values of assessed parameters between groups A and B. Taking into account all patients enrolled to the study AMH correlated significantly with patients' age and plasma levels of FSH at day 3 and day 10 of the cycle). Basic AMH plasma levels in group A correlated negatively with plasma levels of FSH at day 3 and day 10. In group B plasma levels of FSH at day 10 of the cycle also correlated with basic AMH plasma levels. Plasma levels of estradiol at day 10 of the cycle were related inversely with basic AMH plasma levels in group A, but directly in group B. CONCLUSION: It should be recommended to perform the CCCT before infertility treatment. Evaluation of the anti-Müllerian hormone plasma level reflects the results of the CCCT.

A systematic review of tests predicting ovarian reserve and IVF outcome.

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.

Prognostic value of some ovarian reserve tests in poor responders.

BACKGROUND: The objective of this study was to determine the prognostic value of the basal estradiol (E2) and inhibin-B levels, the antral follicle count (AFC), and the clomiphene citrate challenge test (CCCT) of ovarian response in controlled ovarian hyperstimulation (COH), in an outcome with normal follicle-stimulating hormone (FSH) concentration in the early follicular phase of the menstrual cycle. METHODS: Fifty-two patients undergoing IVF treatment were included in the study. Blood samples were collected for assessment of basal E2, FSH, and inhibin-B levels. Transvaginal ultrasound of an unstimulated cycle was performed to determine the mean antral follicle count (AFC). Serum FSH concentration was measured again on day 10 for CCCT performance. RESULTS: The mean values of women's age, and basal and day 10 FSH levels were significantly higher in cancelled cycles than in the control group, whereas basal inhibin-B and AFC were significantly higher in the latter. The mean basal E2 concentration was similar in both groups. The results from the logistic regression analysis show that CCCT (cut-off point FSH > 12.5 mIU/ml; AUCROC = 0.90) was a better single predictor of poor ovarian response than AFC (AUCROC = 0.85) and inhibin-B (AUCROC = 0.79) with a correct prediction for CCCT (86.5%), antral follicle count (84.6%), and for inhibin-B (82.7%). CONCLUSIONS: In women with normal basal FSH level, the determination of E2 has no prognostic value for the outcome of poor responders. However, CCCT, AFC, and inhibin-B tests, when applied separately, produce good prognostic values. CCCT is the best single predictor of poor ovarian response, followed by antral follicle count and basal inhibin-B values. In spite of that, CCCT does not add significantly to the simpler AFC ultrasound test in the prediction of poor ovarian response.

Mucosal cytology in the determination of the pubertal status in girls.

AIM: To assess and validate the diagnostic value of buccal and vaginal smears in the ambulatory care of girls with potential disorders of puberty. METHODS: Smears were obtained from 77 girls who presented for assessment of their pubertal status, stained as described by Papanicolaou, examined for signs of estrogenization according to the method of Schmitt, and compared with the clinical status. RESULTS: Vaginal but not buccal smears reflect accurately the changes of sexual maturation, even more sensitive than single serum hormone measurements. CONCLUSIONS: Vaginal smears represent a valid, reproducible, and well-tolerated diagnostic tool in the ambulatory care of peripubertal girls to identify their estrogen status with high sensitivity and specificity. The decision to perform confirmative but invasive diagnostic procedures can be based on auxology, physical examination, bone age determination, and analysis of vaginal smears.

Climaterio precoce / Premature ovarian failure

Este trabalho aborda o climaterio precoce, ou seja, a perda da funcao ovariana antes dos 40 anos de idade, sob varios aspectos : incidencia, importancia, desenvolvimento ovariano normal...