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.

Estimated Number of Lifetime Ovulatory Years and Its Determinants in Relation to Levels of Circulating Inflammatory Biomarkers.

Reproductive events, such as ovulation, trigger an inflammatory cascade. Few studies have examined their long-term influence on inflammatory profiles. We included 3,393 premenopausal and 3,915 postmenopausal women with intact ovaries/uterus from the Nurses' Health studies (Nurses' Health Study (1989-1990) and Nurses' Health Study II (1996-1999)) in an analysis of the association between lifetime ovulatory years (LOY) and levels of inflammatory biomarkers. We estimated LOY as age at menopause (age at blood collection for premenopausal women) minus age at menarche, subtracting years of oral contraceptive (OC) use and 1 year per pregnancy. After adjustment for other inflammation-related factors (e.g., body mass index, exercise, diet), every 5-year increase in LOY was associated with lower C-reactive protein (CRP) levels in both premenopausal (difference = -11.5%, 95% confidence interval: -15.0, -8.0; P < 0.0001) and postmenopausal (difference = -7.2%, 95% confidence interval: -10.0, -4.3; P < 0.0001) women. Older age at menopause (P = 0.007), earlier menarche (P = 0.007), and shorter duration of OC use (P = 0.002) were associated with lower CRP levels in postmenopausal women, whereas duration of OC use was positively associated with CRP levels in premenopausal women (P < 0.0001). LOY was modestly inversely associated with interleukin 6 in postmenopausal women (P = 0.03). Notably, the associations of CRP with LOY were similar in magnitude to associations with exercise and a healthy diet, though weaker than the association with body mass index. Although many reproductive events induce acute inflammation, increased LOY was associated with lower chronic systemic inflammation even after menopause.

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.

Prediction of the lower serum anti-Müllerian hormone threshold for ovarian stimulation prior to in-vitro fertilization using the Elecsys® AMH assay: a prospective observational study.

BACKGROUND: In assisted reproductive technology, prediction of treatment failure remains a great challenge. The development of more sensitive assays for measuring anti-Müllerian hormone (AMH) has allowed for the possibility to investigate if a lower threshold of AMH can be established predicting very limited or no response to maximal ovarian stimulation. METHODS: A prospective observational multicenter study of 107 women, < 40 years of age with regular menstrual cycle and serum AMH levels ≤ 12 pmol/L, treated with 300 IU/day of HP-hMG in a GnRH-antagonist protocol. AMH was measured before treatment start using the Elecsys® AMH assay by Roche Diagnostics. The ability of AMH to predict follicular development and ovarian response was assessed by receiver operating characteristics (ROC). Furthermore, the relationship between AMH at start of stimulation and cycle outcome was investigated using multivariate logistic regression analysis. RESULTS: Five out of 107 cycles (4.7%) were cancelled due to lack of follicular development and 60/107 (56%) women did not reach the classical hCG criteria for ovulation induction (≥ 3 follicles of ≥17 mm). An AMH threshold of 4 pmol/L predicted failure to reach the classical hCG criteria with 89% specificity and 53% sensitivity and an area under the curve (AUC) of 0.76 (95% CI 0.66-0.85). AMH predicted cycle cancellation due to lack of follicular development, using a cut-off value of 1.5 pmol/L, with a specificity of 96% and sensitivity of 80% (AUC = 0.92, 95% CI 0.79-1.00). A single-unit increase in AMH was associated with a 29% decrease in odds of failure to reach the classical hCG criteria (OR 0.71 95% CI 0.59-0.85, p < 0.01). The lowest AMH value compatible with a live birth was 1.3 pmol/L. CONCLUSIONS: Among women with a limited ovarian reserve, pre-treatment serum AMH levels significantly predicted failure to reach the classical hCG triggering criteria and predicted lack of follicular development using a new sensitive assay, but AMH was not suitable for withholding fertility treatment, as even very low levels were associated with live births. TRIAL REGISTRATION: Not relevant.

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.

Study of variables related to multiple pregnancy in cycles of ovarian Stimulation / Estudio de las variables relacionadas con el embarazo múltiple en ciclos de estimulación ovárica

Introduction: This paper analyzes cycles of ovarian stimulation followed by intrauterine insemination or timed intercourse that resulted in pregnancy. Our objective was to identify characteristics of the patient or ovarian response that are associated with multiple pregnancy. Material and methods: We performed a descriptive retrospective observational study of 261 cycles where pregnancy was achieved by intrauterine insemination or timed intercourse. The sample was obtained from 1,189 infertile couples treated from January 2009 to December 2014. We evaluated features that were potentially associated with multiple pregnancy and dependent on the patient, treatment, and ovarian response. Results: Of all the pregnancies analyzed, 88.9% were singleton and 11.1% multiple (8.4% twins, 2.7% triplet). In the multiple pregnancy group, the average number of intermediate follicles (14-16 mm), follicles measuring ≥ 17 mm, and the total number of follicles on the day human chorionic gonadotropin was administered were higher than for the singleton pregnancy group (p < 0.05). We found no correlation between multiple pregnancy and age, type and diagnosis of infertility, drug used for stimulation, initial and total dose of gonadotropin, number of treatment cycles, and motile sperm count. Conclusions: This study confirms the association between multiple births and increased number of follicles. When follicles were classified by size and multiple pregnancy as twin and triplet, we found that intermediate follicles were significantly associated with twin pregnancy. Consequently, they must be taken into account when deciding to cancel a cycle in order to try to reduce the risk of multiple pregnancy

Introducción: este trabajo analiza los ciclos de estimulación ovárica seguidos de inseminación intrauterina o coito programado que lograron embarazo. El objetivo es identificar las características de la paciente o de la respuesta ovárica asociadas con el embarazo múltiple. Material y métodos: es un estudio observacional retrospectivo descriptivo. Incluye 261 ciclos en los que se ha conseguido embarazo mediante inseminación intrauterina o coito programado. La muestra se ha obtenido de 1.189 parejas infértiles tratadas de enero de 2009 a diciembre de 2014. Se evalúan características potencialmente asociadas con el embarazo múltiple dependientes de la paciente, del tratamiento aplicado y de la respuesta ovárica. Resultados: el 88,9% de los embarazos fueron únicos y el 11,1%, múltiples (8,4% gemelares, 2,7% triples). En el grupo de embarazo múltiple, la media de folículos intermedios (14-16 mm), los folículos con una media de ≥ 17 mm y el total de folículos el día de la gonadotropina coriónica humana fueron mayores respecto al grupo de embarazo único (p < 0,05). No hemos hallado correlación entre embarazo múltiple y edad de la paciente, tipo y diagnóstico de esterilidad, fármaco utilizado en la estimulación, dosis inicial y total de gonadotropina, número de ciclos de tratamiento y recuento de espermatozoides móviles postcapacitación. Conclusiones: este estudio confirma la asociación entre embarazo múltiple y mayor número de folículos. Desglosando los folículos por su tamaño y el embarazo múltiple en gemelar y triple, los folículos intermedios se asocian significativamente a embarazo gemelar, por lo que deben ser tenidos en cuenta en la decisión de cancelación para intentar disminuir el riesgo de embarazo múltiple

A propósito de un caso: trombosis yugular interna espontánea en gestante sometida a tratamiento de fertilidad / On the subject of a case: Spontaneous internal jugular thrombosis in pregnant women undergoing fertility treatment

La trombosis venosa yugular interna constituye una causa poco común de trombosis venosa profunda. Existen factores de riesgo como el embarazo y la inducción de la ovulación con gonadotropinas en pacientes sometidas a tratamientos de fertilidad, normalmente asociada a síndrome de hiperestimulación ovárica. Se describe el caso de una paciente de 35 años con antecedentes personales de endometriosis. Quedó gestante tras un único ciclo de fecundación in vitro con semen de donante por pareja homosexual. Desarrolló un síndrome de hiperestimulación ovárica severo que requirió culdocentesis evacuadora, evolucionando favorablemente. En la semana 9+6 comienza con dolor y edema en cara lateral derecha cervical, diagnosticándose mediante ecografía doppler de trombo a nivel de la vena yugular derecha y tercio proximal de subclavia ipsilateral. Se instauró tratamiento con heparina de bajo peso molecular con monitorización de los niveles de factor anti-Xa y realizándose un seguimiento multidisciplinar seriado. Se finalizó el embarazo en semana 37+2 mediante estimulación produciéndose un parto eutócico. Tras el parto la paciente deberá mantener el tratamiento con heparina de bajo peso molecular recomendándose un estudio de trombofilia. Si bien el embarazo, puerperio y el tratamiento hormonal están descritos como factores predisponentes para eventos trombóticos, es poco frecuente que sean la única causa. No obstante, si tras un tratamiento hormonal la paciente desarrolla un síndrome de hiperestimulación ovárica se debe mantener la tromboprofilaxis hasta la semana 12 de gestación. Ante la presencia de trombosis durante el embarazo después de una estimulación ovárica, sobre todo si la localización de la misma es atípica, sería recomendable realizar una evaluación de trombofilia (AU)

The internal jugular vein thrombosis is an uncommon cause of deep vein thrombosis. There are risk factors such as pregnancy and ovulation induction with gonadotropins in patients undergoing fertility treatments, typically associated with ovarian hyperstimulation syndrome. The case of a patient of 35 years with a history of endometriosis is described. She was pregnant after a single cycle of IVF with donor sperm by homosexual couples. He developed severe ovarian hyperstimulation syndrome requiring evacuadora culdocentesis, evolving favorably. In week 9 + 6 begins with pain and swelling in right lateral cervical, diagnosed by Doppler ultrasound thrombus at the level of the right jugular vein and proximal third of ipsilateral subclavian. Treatment was established with low molecular weight heparin with monitoring the levels of anti-factor Xa and performing a serial multidisciplinary follow. Pregnancy ended in week 37 + 2 producing a vaginal delivery. After delivery the patient should continue treatment with low molecular weight heparin and is recommended a study of thrombophilia. While pregnancy, postpartum and hormone treatment are described as predisposing factors for thrombotic events, it is rare that they are the only cause. However, if after hormone treatment, the patient develops ovarian hyperstimulation syndrome thromboprophylaxis should be maintained until the 12th week of gestation. In the presence of thrombosis during pregnancy after ovarian stimulation, especially if the location of it is atypical, it would be advisable to make an assessment of thrombophilia (AU)

Utilidad clínica de la hormona antimülleriana en la predicción de la edad ovárica en España / Clinical use of antimüllerian hormone to predict ovarian age in Spain

Objetivo: la hormona antimülleriana es un marcador clínico de la reserva ovárica pero no disponemos de sus valores de referencia en la población española. Se han determinado sus valores de normalidad en relación a la edad en una amplia muestra de población española. Sujetos y métodos: se estudiaron 10.443 mujeres (edad 20-45 años). Todas las determinaciones séricas de hormona antimülleriana se realizaron mediante un test de ELISA (hormona antimülleriana Gen II ELISA assay; Beckman Coulter, Brea, CA, USA). Resultados: la edad media fue 36,6 ± 4,3 años. Los niveles de la hormona antimülleriana se correlacionaron inversamente con la edad (r = −0,35; p < 0,001). La edad ovárica aumentaba 1 año por cada descenso medio de 0,2 ng/ml de hormona antimülleriana. Se obtuvieron diferencias significativas en los valores de hormona antimülleriana entre Cataluña, Baleares y Andalucía. Conclusiones: este estudio ofrece estimaciones de los valores de referencia de hormona antimülleriana en función de la edad y contribuye a determinar con mayor precisión la reserva ovárica de las mujeres españolas (AU)

Objetives: Antimüllerian hormone is considered clinically useful in the evaluation of ovarian reserve, and few data exists regarding its distribution in the Spanish population. We determine normality values of antimüllerian hormone related to age in a large Spanish community cohort. Subjects and methods: We study 10,443 women (aged 20-45). Antimüllerian hormone values were analysed using an ELISA assay (antimüllerian hormone Gen II ELISA assay; Beckman Coulter, Brea, CA, USA). Results: The mean age of women was 36.6 ± 4.3 years. Antimüllerian hormone values were inversely correlated with age (r = −0.35; p < 0.001). From the regression equation, the estimated yearly decrease in antimüllerian hormone was 0.2 ng/ml. Significant differences were obtained in mean values of antimüllerian hormone among Cataluña, Baleares, and Andalucía. Conclusions: This study reports the distribution of antimüllerian hormone values in different age groups in Spain, and contribute to determine the ovarian reserve in Spanish women (AU)

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.

The BOC ELISA, a ruminant-specific AMH immunoassay, improves the determination of plasma AMH concentration and its correlation with embryo production in cattle.

Plasma anti-Müllerian hormone (AMH) concentrations have been recently found to be predictive of the number of embryos recovered after FSH superovulatory treatment in the cow. However, the sensitivity of the Active Müllerian-inhibiting substance/AMH ELISA (ref. 10-14400; DSL-Beckman-Coulter) used to make these measurements in bovine plasma samples is low because it was developed to measure human AMH levels. To overcome this limitation, we developed an immunoassay specific for the bovine (B), ovine (O), and caprine (C) species, the bovine-ovine-caprine (BOC) ELISA. For this purpose, we produced recombinant bovine AMH for standardization, and we used monoclonal antibodies raised against bovine AMH, previously prepared by our laboratory. We evaluated the precision, accuracy, specificity, limit of detection, and functional sensitivity of the assay. The intra-assay coefficient of variation ranged between 3.4% and 11.3% for AMH concentrations between 23.68 and 1.74 ng/mL, and the interassay coefficient of variation ranged between 4.8% and 20.5% for concentrations between 25.53 and 1.42 ng/mL, respectively. The assay displayed a good linearity, had a detection limit of 0.4 ng/mL and a functional sensitivity of 1.4 ng/mL. It also cross-reacted with ovine and caprine AMHs. Both the mean and median AMH levels measured in 40 cow plasma samples using the BOC ELISA were approximately 44 fold higher than the mean and median AMH levels measured with the Active Müllerian-inhibiting substance/AMH ELISA. Moreover, a higher correlation was observed between the average number of embryos recovered from each cow after superovulatory treatment and AMH concentrations measured with the BOC ELISA. This BOC ELISA provides a very efficient tool for evaluating the ovarian follicular reserve of cows and predicting their embryo production capacity.

Role of ovarian reserve markers, antimüllerian hormone and antral follicle count, as aneuploidy markers in ongoing pregnancies and miscarriages.

OBJECTIVE: To assess the role of two ovarian reserve markers, antimüllerian hormone (AMH) and antral follicle count (AFC), as markers of the background risk for fetal trisomy. DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENT(S): Assessment was carried out either in ongoing pregnancies or miscarriages in our center. INTERVENTION(S): AFC was assessed transvaginally during a routine (11-13 weeks) or referral scan. AMH was determined either during the first-trimester maternal serum markers assessment or in cases referred for chorionic villi sampling after the invasive procedure. MAIN OUTCOME MEASURE(S): AMH reference ranges were constructed according to maternal age, and AMH- and AFC-derived ovarian ages were compared among three different cytogenetic groups (normal karyotype, autosomal trisomies, and other chromosomal anomalies) in both ongoing pregnancies and miscarriages. RESULT(S): In autosomal trisomies, the median AFC-derived ovarian age was 3-5 years above the median maternal age. No differences were observed between AMH-derived ovarian age and maternal age. CONCLUSION(S): AFC-derived ovarian biologic age reflects a more precise background risk for fetal aneuploidy that is not observed for AMH-derived age.

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.

Predictive value of antral follicle count and anti-Müllerian hormone for follicle and oocyte developmental competence during the early prepubertal period in a sheep model.

Circulating anti-Müllerian hormone (AMH) and antral follicle count (AFC) are addressed as suitable markers of oocyte quantity and quality during adulthood. To investigate whether AFC and circulating AMH could predict follicle development and oocyte quality during the prepubertal period we used 40-day-old ewe lambs with high, intermediate and low AFC (≥30, 16-29 and≤15 follicles respectively). The analysis of the response to the exogenous FSH ovarian reserve test showed a positive correlation between AFC, AMH plasma levels, total follicle number and the number of large follicles (≥3mm) grown after exogenous FSH administration. The incorporation of abattoir-derived oocytes collected from ovaries with different AFC in an in vitro embryo production system showed that a high AFC can predict oocyte quality in prepubertal ovaries, reflecting an ovarian status suitable for follicular development. The histological quantification of the ovarian reserve evidenced that AFC was not predictive of differences in either the number of healthy follicles or the size of the primordial follicle pool in prepubertal ovaries. Further studies are needed to investigate the implication on the reproductive performance of the significant inter-individual differences found in the present study in AFC and circulating AMH in the early prepubertal period.

Ovarian reserve test: an impartial means to resolve the mismatch between chronological and biological age in the assessment of female reproductive chances.

Nowadays, the ovarian reserve (OR) is considered more important than chronological age to estimate female reproductive capability. We conducted a retrospective, observational, and cohort study in order to detect the best predictor marker of OR, ovarian response, chances to obtain high-quality embryos, and pregnancy after in vitro fertilization (IVF) cycle in elderly women. For all eligible patients (aged between 40 and 50 and admitted to their first IVF cycle for primary infertility), we investigated the biochemical parameters and ultrasound aspects of ovaries and how they affected IVF outcomes. Age, basal follicle-stimulating hormone, basal luteinizing hormone, and basal-17ß-estradiol are better related to the dose of gonadotropin used during a controlled ovarian stimulation cycle. Basal anti-Müllerian hormone (AMH), antral follicular count (AFC), and maximum serum level of 17ß-estradiol before pickup resulted the best predictors of chances to retrieve at least 6 oocytes (at least 3 in metaphase II) and to have at least 1 to 3 embryos. The basal AMH, AFC and maximum serum level of 17ß-estradiol before pickup continue to show higher correlation to pregnancy rate. The maximum endometrial thickness at pickup resulted important to predict the pregnancy rate and the chances to detect ongoing pregnancy. It seems mandatory to well define the ovarian biological age rather than the chronological one in women older than 40 years of age in order to give the best counseling and to choose the most appropriate IVF protocols.

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.