Article

Probability of live birth in women with extremely low anti-Mullerian hormone concentrations

September 2013
Reproductive BioMedicine Online 28(1)

DOI:10.1016/j.rbmo.2013.09.017

Source
PubMed

Authors:

Krzysztof Lukaszuk

Medical University of Gdansk

Michał Kunicki

Joanna Liss

Invicta

Show all 5 authorsHide

The aim of the present study was to investigate the clinical pregnancy and live birth rates in women with extremely low (⩽0.4ng/ml) anti-Müllerian hormone (AMH) concentrations. The study included 101 women (188 cycles) with extremely low AMH concentrations undergoing IVF cycles and compared the number of live births in women with low AMH. Moreover, the study compared the number of live births in women with or without endometriosis stage III/IV. Fourteen clinical pregnancies and 14 live births (including one pair of twins) were recorded; one woman miscarried. Significantly higher clinical pregnancy (P=0.046) and live birth rates (P=0.018) were found in women aged <35 years compared with older women. AMH concentration did not differ significantly between women with or without endometriosis and there were six live births in women with endometriosis. This was not significantly different from the rate in healthy women. It is concluded that live births are possible in women with extremely low AMH concentrations. The presence of endometriosis stage III/IV did not affect live birth rates in women with extremely low AMH concentrations although an important limitation of the study is the small number of women included who were affected by that disease. The aim of the present study was to investigate the clinical pregnancy and live birth rates in women with extremely low (⩽0.4ng/ml) anti-Müllerian hormone (AMH) concentrations. Moreover, we compared the number of live births in women with or without endometriosis stage III/IV. We concluded that, in women with extremely low AMH concentrations, live births are possible. The presence of endometriosis stage III/IV did not affect live birth rates in women with extremely low AMH concentrations, although the strong limitation of the study is that it included only a small number of women affected by that disease.

The value of Anti-Müllerian hormone in low and extremely low ovarian reserve in relation to live birth after in vitro fertilization

Article

Feb 2016

The correlation of AMH with clinical outcomes of patients with IVF- ICSI failures according to the ovarian response

Article

Full-text available

Jan 2024

Anti-Mullerian Hormone (AMH) is considered as the most important biomarkers of ovarian reserve, its response and even as predictor of IVF outcomes. However, until now, the correlation of AMH to IVF outcomes is still debated depending on AMH cutoff. Couples with IVF failures are representing the most critic population to understand using different biomarkers in order to predict the results and suggest wisely a personalized management algorithm for them, especially those with low and high AMH. For this reason, our retrospective cross-sectional study, 147 patients were included with women's mean age of 35 years old (22-40 years) with at least 2 IVF-ICSI failures and undergoing IVF-ICSI fresh cycle, representing an idiopathic infertility, who were divided into 3 groups: Group PR (Poor Response; Patients with less than 5 retrieved oocytes (n=47)), Group NR (Normal Response; Patients presenting between 5 and 10 retrieved oocytes (n=55)), and Group HR (Hyper-Response; Patients with more than 10 retrieved oocytes (n=45)). Then, each group was studied based on the female age. As results, AMH differences were significant between the 3 groups PR, NR and HR respectively (0.54 ± 0.76, 2.13±2.10, 4.03 ± 2.82). The PR showed 16% for pregnancy rate while NR and HR could have 53% and 39% respectively. Even the group with extreme low AMH (<0.5ng/ml) could to reach 17% of pregnancy rate. AMH showed significant correlation with AFC (r=0.67) but non-significant with the number of IVF failures (r=-0.03). Those results could to show the correlation of AMH to clinical outcomes especially the pregnancy rate whatever is the ovarian response, while even the category with extreme low AMH could succeed the IVF process clinically while it is generally ignored. Those results are calling in need to develop more the predictive model of AMH and AFC correlated to ovarian response, of clinical outcomes for patients with IVF failures for deeper understanding of risk factors.

The correlation of AMH with clinical outcomes of patients with IVF- ICSI failures according to the ovarian response

Article

Full-text available

Jan 2024

Fertility Counseling in BRCA1/2-Mutated Women with Breast Cancer and Healthy Individuals

Article

Full-text available

Jul 2022

Breast cancer is the most commonly diagnosed cancer worldwide and the fifth leading cause of cancer death. In 2020, there were 2.3 million new cases, and 685,000 women died from it. Breast cancer among young women under 40 years of age accounts for 5% to 10% of all cases of this cancer. The greater availability of multi-gene sequence analysis by next-generation sequencing has improved diagnosis and, consequently, the possibility of using appropriate therapeutic approaches in BRCA1/2 gene mutation carriers. Treatment of young breast cancer patients affects their reproductive potential by reducing ovarian reserve. It can lead to reversible or permanent premature menopause, decreased libido, and other symptoms of sex hormone deficiency. This requires that, in addition to oncological treatment, patients are offered genetic counseling, oncofertility, psychological assistance, and sexological counseling. Given the number of BRCA1/2 gene mutation carriers among young breast cancer patients, but also thanks to growing public awareness, among their healthy family members planning offspring, the possibility of benefiting from preimplantation testing and performing cancer-risk-reduction procedures: RRM (risk-reducing mastectomy) and RRSO (risk-reducing salpingo-oophorectomy) significantly increase the chance of a genetically burdened person living a healthy life and giving birth to a child not burdened by the parent’s germline mutation. The goal of this paper is to show methods and examples of fertility counselling for BRCA1/2 gene mutation carriers, including both patients already affected by cancer and healthy individuals.

Testing ovarian reserve in pre-menopausal women: Why, whom and how?

Article

Nov 2017
MATURITAS

Numerous social and environmental factors (environmental hazards, social factors such as education and career, higher economic status desired before the decision is made to have children) influence a women's decision to postpone pregnancy until late reproductive age. In turn, age is related to a fall in ovarian reserve. The main goal of testing ovarian reserve is the identification of women with so-called diminished ovarian reserve (DOR). Additionally, it provides assistance in the counselling of women who are planning to use assisted reproductive techniques (ART). This review examines current methods of testing ovarian reserve and their application. The most useful methods of assessing ovarian reserve are ultrasonographic count of ovarian antral follicles (AFC) and serum tests of both the anti-Müllerian hormone (AMH) level and the third-day level of follicle stimulating hormone (FSH). However, there are limitations to the currently used methods of testing ovarian reserve, especially in relation to their specificity and sensitivity. It is also difficult to predict egg quality based on these tests. The value of screening programmes of ovarian reserve is yet to be determined.

Antimullerian hormone (AMH) level and IVF/ICSI cycle outcome in expected poor responders

Article

Full-text available

Nov 2017

Objective to study AMH level effect on IVF/ICSI cycle outcome in expected poor responders undergoing ART. Design retrospective cohort study. Setting IVF unit at king Abdulaziz medical city, Riyadh, KSA. Materials and methods 258 patients expected to be poor responders according to Bolonga criteria (aged >37or previous poor ovarian response or patients with decreased ovarian reserve) had their serum AMH level obtained and underwent IVF/ICSI cycles between April 2013 to April 2015. Outcome pregnancy and cancellation rates. Results patients were divided into three groups according to their AMH level, 60 Patients with AMH level ≤2.8, 98 patients with AMH level 2.9-14.9, and 100 patients with AMH level >15 pmol/l. Patients with lowest AMH had lowest AFC, highest FSH, and lowest number of previous delivery. Lowest AMH patients had lowest number of oocytes collected (p < .0001), lowest pregnancy rate (p = .001), and highest cancellation rate (p < .001). The receiver operating characteristic (ROC) curve analysis was used to establish the cut-off value for serum AMH level in predicting cancellation of ART cycle. It revealed a cutoff point of 2.8 pmol/L with sensitivity of 85% and specificity of 45% (DeLong SE = 0.04: CI 0.58-0.75). ROC of AMH level and pregnancy prediction showed a cut off point of 16.2 pmol/L with sensitivity 54% and specificity of 66% (DeLong SE = 0.04: CI 0.53-0.69). Conclusion Low AMH level in expected poor responders in ART cycles had lower pregnancy rate and higher cancellation rate.

The effects of both serum and follicular fluid anti-mullerian hormone on rate of the oocytes yield, fertilization & clinical pregnancy

Article

Full-text available

Nov 2016

Safak Ozdemirci

Objective: The objective of this study was to evaluate the relationship between oocyte yield, fertilization, and clinical pregnancy (CP), and anti-Mullerian hormone (AMH) level in serum and follicular fluid during in vitro fertilization treatment. Methods: Forty-four infertile women who underwent IVF treatment using multiagonist protocol were included in this study. Baseline level of AMH in serum and follicular fluid was measured on third day of menstrual cycle. AMH level in serum and follicular fluid was then measured again on day of oocyte pick-up. Pearson correlation and binary regression tests were used for statistical analysis. For Type 1 error, p=5% was selected as cut-off value for statistical significance. Results: Serum AMH level was positively correlated with total number of oocytes retrieved and rate of fertilization and CP (r=0.397, p=0.008; r=0.401, p=0.007; and r=0.382, p=0.011, respectively). There was significantly negative correlation between serum level of follicle-stimulating hormone (FSH) and fertilization rate (r=-0.320; p=0.034), as well as serum FSH level and CP rate (r=-0.308; p=0.042). There were no significant correlations between AMH level in follicular fluid and IVF treatment outcomes. Conclusion: Serum AMH levels may be more reliable for prediction of total number of oocytes retrieved and rate of fertilization and CP than AMH levels in follicular fluid.

IVF results in patients with very low serum AMH are significantly affected by chonological age

Article

Full-text available

May 2016
J ASSIST REPROD GEN

Purpose: The aims of this study were to assess the outcome of in vitro fertilization (IVF) in women with very low circulating anti-müllerian hormone (AMH) and to investigate factors affecting their probability of pregnancy. Methods: The outcome of 448 IVF cycles in 361 women with circulating AMH <0.5 ng/ml was retrospectively analyzed. Results: Cycle cancellation rate was 14.5 %; patients whose cycle was cancelled had significantly lower AMH than women who reached oocyte pickup (OPU). Among those who reached OPU, age significantly affected the success rate: despite comparable AMH levels, patients below 35 years obtained significantly more oocytes and a better clinical pregnancy rate (CPR)/OPU than patients aged 35-39 or 40-43 (31 % vs. 23.2 % vs. 10.2 %, respectively; p = 0.001). Differently, comparable IVF results were observed stratifying patients for AMH levels in the range 0.14-0.49 ng/ml. Multivariable logistic regression analysis confirmed that the probability of pregnancy was significantly affected by age, but not by small differences in AMH level. Conclusions: Women with very low (<0.5 ng/ml) AMH levels undergoing IVF still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Very low AMH levels are associated with a relevant risk of cycle cancellation but should not be considered a reason to exclude a couple from IVF.

The Effect of Endometriosis on In Vitro Fertilization Outcomes: A Systematic Review and Meta-Analysis

Article

Full-text available

Dec 2024

Objectives: The purpose of this study was to evaluate the impact of endometriosis on various outcomes of in vitro fertilization (IVF), including live birth rates, clinical pregnancy rates, fertilization rates, and implantation rates, through a systematic review and meta-analysis. Methods: Systematic searches were carried out using PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, EMBASE, and Web of Science from January 2010 to November 2023. Studies comparing IVF outcomes in women with and without endometriosis were included. The primary outcome was live birth rate; secondary outcomes included clinical pregnancy, fertilization, and implantation rates. Data were extracted and analyzed using odds ratio (OR) and 95% confidence interval (CI) with fixed or random-effects models, depending on heterogeneity. Results: From 1340 studies initially identified, 40 studies met the inclusion criteria, encompassing 8970 women with endometriosis and 42,946 control participants. There were no significant differences between the endometriosis and control groups in terms of live birth rate (OR 1.03, 95% CI 0.75–1.41, p = 0.84), clinical pregnancy rate (OR 0.86, 95% CI 0.72–1.02, p = 0.1), or fertilization rate (OR 0.96, 95% CI 0.79–1.15, p = 0.64). However, endometriosis was associated with a significantly lower implantation rate (OR 0.85, 95% CI 0.74–0.97, p = 0.02). Conclusions: Endometriosis significantly negatively affects implantation rates in women undergoing IVF, despite the absence of significant differences in live birth, clinical pregnancy, and fertilization rates. Further research is needed to evaluate the impact of different stages of endometriosis on IVF outcomes and to develop optimized management protocols for these patients.

Screening for diminished ovarian reserve in Portugal: a cost-saving answer to shorten the fertility journey

Article

Full-text available

Jun 2023

Aim: Assess the budget impact of nationwide screening for diminished ovarian reserve (OR), via anti-Mu¨ llerian hormone (AMH) levels, to the Portugal National Health System (NHS). Patients & methods: The clinical journey was determined using literature and the family planning decision-making process/response using survey results. A panel of four local clinicians validated all assumptions/inputs. Results: Screening for OR led to an expected savings of € 9.4 million for the NHS, driven by a 24% reduction in medically assisted reproduction (MAR) use. When needed, referral for MAR was earlier and more women used first-line versus second-line techniques. The model estimated a 12% decrease in failure. Conclusion: This model shows AMH screening may allow more informed decisions, leading to a shorter fertility journey, more efficient use of treatments, and substantial cost-savings for the NHS.

FSH versus AMH: age-related relevance to ICSI results

Article

Full-text available

Dec 2021

Abstract Background Women’s fecundity is known to decrease with the increase in chronologic age. Several biomarkers of the ovarian reserve, including follicle stimulating hormone (FSH), anti Müllerian hormone (AMH), have been proposed as possible predictors for the response to controlled ovarian stimulation (COS). Although there are assumptions indicating that the relationship between age and ovarian reserve is highly variable and the potential different validity of ovarian reserve markers in women in different age groups remains to be demonstrated. The purpose of our study was evaluating FSH and AMH as potential predictors of response to controlled ovarian stimulation and prediction of intracytoplasmic sperm injection (ICSI) outcome according to age. This prospective study has been carried out on 218 women having ICSI cycles. Cases were divided into two groups, group 1 (n 148), their age

Anti-Müllerian hormone is correlated with cumulative live birth in minimal ovarian stimulation with clomiphene citrate: a retrospective cohort study

Article

Full-text available

Nov 2020

Background Several studies have investigated the correlation between the serum anti-Müllerian hormone (AMH) level and in vitro fertilization (IVF) outcomes in controlled ovarian stimulation cycles; however, studies regarding the correlation of the serum AMH level with IVF outcomes in minimal ovarian stimulation cycles remain limited. In this study, we aimed to analyze the correlation of the serum AMH level with ovarian responsiveness, embryonic outcomes, and cumulative live birth rates in clomiphene citrate (CC)-based minimal ovarian stimulation cycles. Methods Clinical records of 689 women whose entire ovarian stimulation regimen consisted solely of minimal stimulation cycle IVF using CC alone from November 2017 to October 2019 were retrospectively reviewed. The association between IVF outcomes and the serum AMH level before the initiation of the first fertility treatment was analyzed. Furthermore, the correlation of the serum AMH level with cumulative live birth rates after IVF treatment was assessed. The Cochran-Armitage test, Pearson’s chi-squared test, Spearman rank correlation test, Student’s t-test, one-way analysis of variance, logistic regression analysis, Kaplan-Meier method and Cox proportional hazards model were used to analyze the data. Results The serum AMH level positively correlated with the number of retrieved oocytes, blastocyst formation rate, blastocyst cryopreservation rate, and live birth rate per oocyte retrieval in CC-based minimal ovarian stimulation cycles without any exogenous gonadotropin administration. Furthermore, the cumulative live birth rate and treatment period required for conceiving were strongly associated with the serum AMH level at the initiation of fertility treatment. Conclusions A low serum AMH level correlated with low ovarian responsiveness, impaired pre-implantation embryonic development, and decreased cumulative live birth rate in CC-based minimal ovarian stimulation cycles. Therefore, the cycle success rate would be predicted by measuring the serum AMH level in minimal ovarian stimulation with CC alone.

Assessment of the relationship of basal serum anti mullerian hormone levels and maternal age with pregnancy out come in patients undergoing icsi

Article

Jan 2020

The effects of maternal age on pregnancy outcomes are well known, particularly the association of advanced maternal age with poor ART results. Decreased ovarian reserve and decreased endometrial receptivity resulting from increased age are likely reasons for this observed reduction in fertility. AMH plays a role in regulating ovarian activity. Additionally, it inhibits initiation of the development of primordial follicles and the selection of a high number of follicles by decreasing the follicles' sensitivity to follicle stimulating hormone (FSH). The aim of the study is to assess the relationship of basal serum antimullerian hormone level and maternal age with oocyte quality and embryo quality and pregnancy outcomes in patient undergoing ICSI. The current observational prospective study included 100 infertile women who underwent ICSI at The High Institute of Infertility Diagnosis and Assisted Reproductive Technology/AL-Nahrian University, for the period from September 2018 to June 2019. All patients were treated with a GnRH antagonist protocol. Hormonal assay was performed using ELISA technique (BioTek, USA and CAT# AM448T, CalbiotechInc, CA, USA). At the end of the ICSI cycles 29 women have succeeded to get positive clinical pregnancy, while 71 women unfortunately have failed to get pregnant; thus the clinical pregnancy rate was 29 %. When subfertile women were classified into 4 subgroups, positive pregnancy outcome was significantly highest in women with age ≤ 33 and AMH > 1.63 (73.1 %), followed by women with age ≤ 33 and AMH ≤ 1.63 (21.7 %), then women with age > 33 and AMH ≤ 1.63 (9.1 %) and lastly by women with age > 33 and AMH > 1.63 (8.7 %). Age less than 33 and serum anti-mullerian hormone (AMH) levelof > 1.63 ng/ml are the best predictor of pregnancy in subfertile women undergoing intracytoplasmic sperm injection (ICSI).

Is Fertility Affected in Women of Childbearing Age with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder?

Article

Full-text available

Nov 2020
J MOL NEUROSCI

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system (CNS), which is more prevalent among women of childbearing age. Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease of the CNS with similar prevalence features to MS and has recently been considered a different entity from MS. Measuring ovarian reserve is one way of evaluating fertility. Anti-Müllerian hormone (AMH) is a peptide hormone produced by ovarian granulosa cells of early follicles and is considered to be a marker for ovarian reserve. With MS and NMOSD predominance in young women, the present study aimed to address the possibility of these diseases affecting fertility by measuring AMH levels in MS and NMOSD patients and comparing it with healthy controls. The present study included 23 relapsing-remitting MS (RRMS) patients, 23 seronegative NMOSD patients, and 23 healthy age-matched controls between 18 and 45 years of age. Serum samples of the three groups were collected, and the AMH levels were measured with AMH Gen II Enzyme-Linked Immunosorbent Assay, Beckman Coulter kit. In the present study, the AMH levels did not differ significantly between the groups (p = 0.996). The mean AMH in the RRMS group was 3.59 ± 0.55 ng/ml compared with the mean of 3.60 ± 0.50 ng/ml in healthy controls. The mean AMH levels in the NMOSD group were 3.66 ± 0.61 ng/ml. Lower levels of AMH were found to be negatively associated with annualized relapse rate (in both groups of patients) and MS severity score. However, the difference was not significant. In NMOSD patients, the serum levels of AMH were negatively associated with disease duration (r = − 0.42, p = 0.023). There had been a significant negative correlation between mean AMH serum levels with Expanded Disability Status Scale (EDSS) at the time of diagnosis and at the time of study in the NMOSD group (r = − 0.402, p = 0.03 and r = − 0.457, p = 0.014, respectively). There was not a significant difference in mean serum AMH levels between RRMS and NMOSD patients compared with that of healthy controls. Further studies with larger sample sizes should be conducted, which take more variables affecting fertility in women with either RRMS or NMOSD into account to put an end to the controversial issue of fertility in this area.

Influence of age on response to controlled ovarian stimulation in women with low levels of serum anti-Müllerian hormone

Article

Full-text available

Mar 2020

This study aims at detecting and evaluating differences in quantitative response to controlled ovarian stimulation (COS) with high doses of gonadotropins in women with low serum anti-Müllerian hormone (AMH). About 369 first cycles in a real-life scenario in women between 21 and 43 years old and with AMH ≤0.9 ng/ml were analyzed. Older women had a significantly worse outcome with respect to young women, not only qualitatively, but also in terms of quantitative ovarian response to COS [odd ratio (OR) to obtain at least three MII oocytes with each increasing year of female age: 0.89, 95% CI: 0.85 − 0.94; p < .001]. This study endorses that age is a significant factor when counseling patients with low AMH. AMH levels per se are not a reason to exclude patients from a COS treatment, since pregnancy and live birth can be achieved, especially in younger patients. However, with an AMH equally low, the ovarian response worsens with age, making questionable the effectiveness of a stimulation with high-dose gonadotropins in the older subgroup.

Live birth rate after IVF/ICSI in women with low and extremely low AMH: an age-matched controlled study

Article

Full-text available

Dec 2020

Background An age-matched controlled study, to assess the outcome of IVF/ICSI in low and extremely low AMH levels in different age groups by comparing the live birth rate Materials and methods An age-matched controlled study was done at the Egyptian IVF center, Cairo, Egypt, including 306 infertile women with low AMH levels undergoing IVF/ICSI and an age-matched number of women with normal AMH. The live birth rate in the different age groups according to the AMH level was compared. Results There was no significant difference between LBR in the extremely low AMH arm (11.43%) and low AMH (16.4%) ( P = 0.24). The LBR was 30.4% in women with normal AMH as compared to 14.7% in all women with AMH below 1 pg/ml ( P = 0.002). The LBR was significantly higher in women below the age of 35 years and women of 35-40 years with normal AMH (33.2% and 31.7%) as compared to LBR in the corresponding age groups with low AMH (18.6% and 13.3%). Conclusions There was no difference in the outcome of IVF between patients with low and extremely low AMH levels. Women with normal AMH level resulted in a higher pregnancy rate as compared to women with low AMH level in the same age group. Age is important in determining prognosis of IVF in patients with low levels of AMH.

Anti-Müllerian hormone levels in recurrent embryonic miscarriage patients are frequently abnormal, and may affect pregnancy outcomes

Article

Mar 2019

This prospective cohort study measured anti-Müllerian hormone (AMH) levels in recurrent miscarriage (RM) patients, compared them to a normal population, and assessed the pregnancy outcomes. The RM patients demonstrated AMH levels that were significantly lower than the normal population, both in women aged ≤35 years, and those aged >35 years. AMH percentiles were found to be significantly lower in the study group of RM patients ≤35 years (p< .004) in the 5th and 50th percentiles, and in all percentiles in women >35 years (p< .03), were compared to women from a normal population. Serum AMH levels may reflect quality, and quantity of the remaining oocytes in these patients, and RM patients may have a low ovarian reserve, and a potentially poor oocyte quality, as shown by low circulating AMH. The evaluation of AMH levels in a RM work up may allow realistic counselling and possible ART referral in RM patients. • Impact statement • What is already known on this subject? There is some evidence to show that low AMH levels are associated with recurrent miscarriages and this is thought to be due to a decreased oocyte quality. The AMH levels are lower in the patients with endometriosis, and are often significantly higher in the patients with polycystic ovarian syndrome. Both conditions are independently associated with miscarriages. • What the results of this study add? Anti-Müllerian hormone (AMH) levels were found to be significantly lower in recurrent miscarriage patients, compared to a normal population. This may be another factor contributing to miscarriages. The spontaneous pregnancy rates in the miscarriage group significantly improved with increasing AMH levels. This may confirm that patients with low AMH levels have poorer quality oocytes, and thus may be considered ‘sub-fertile’. It was also found that the utilisation of assisted reproductive technologies (ART) to achieve a pregnancy was significantly reduced in the groups with a higher serum AMH. • What the implications are of these findings for clinical practice and/or further research? Serum AMH levels should be offered to all patients as part of a recurrent miscarriage work up. Detecting the low AMH levels and counselling the patients on these findings may allow them the option of accessing ART. ART may have the ability to expedite conception rates, and with pre-implantation genetic analyses, could possibly select the embryos with the greatest chance of survival. Further research is needed to establish how the decreased AMH levels contribute to recurrent miscarriages.

Anti-müllerian hormone as an fertility indicator in women of late reproductive age

Article

Jan 2018

A modern approach to the management of patients candidate to assisted reproductive technologies

Article

Sep 2017
Minerva Ginecol

The growing use of Assisted Reproductive Technologies (ART) and the incorrect information from mass media, determined in the public the wrong idea that the right moment of life for programming a pregnancy can be delayed well beyond the physiological fertile age. Spare and insufficient health authorities' interventions are driven to explain to the general population the reduction of the fertility potential of couples and particularly of women with advancing age. This situation, characterized by more and more women seeking for pregnancy after age 38-40 imposes to specialists in Reproductive Medicine an honest and transparent counselling. Today, more than ever, it is pertinent to talk about the need of an "ethic approach to ART", by which the specialist takes care of all the aspects inherent to infertility, such as the strong motivations of the couples in searching a child, the wrong perception of ART infallibility, the incorrect advertising in the mass media about the pregnancy of elderly actresses and show-girls, and finally, the enormous amount of commercial interests revolving around the "business" of IVF. In this context, the ideal policy that an ART centre should adopt entails the correct and rapid identification of the characteristics of the couple, the exploitation of women ovarian reserve to obtain the right number of high quality oocytes, the protection of patients' health, the identification of the embryos with the highest chances of implantation and the reduction of the time to pregnancy. Here we analyse how to obtain each of these goals, through a literature review and expert clinical opinion.

Qualitative and Quantitative Analysis of Proteome and Peptidome of Human Follicular Fluid Using Multiple Samples from Single Donor with LC-MS and SWATH Methodology

Article

Jun 2017

Human follicular fluid (hFF) is a natural environment of oocyte maturation, and some components of hFF could be used to judge oocyte capability for fertilization and further development. In our pilot small scale study three samples from four donors (12 samples in total) were analyzed to determine which hFF proteins/peptides could be used to differentiate individual oocytes and which are patient specific. Ultrafiltration was used to fractionate hFF to High Molecular Weight (HMW) – proteome (>10kDa) and Low Molecular Weight (LMW) – peptidome (<10 kDa) fractions. HMW and LMW compositions were analyzed using LC-MS in SWATH data acquisition and processing methodology. In total we were able to identify 158 proteins, from which 59 were never reported before as hFF components. 55 (45 not reported before) proteins were found by analyzing LMW fraction, 67 (14 not reported before) were found by analyzing HMW fraction, and 36 were identified in both fractions of hFF. We were able to perform quantitative analysis for 72 proteins from HMW fraction of hFF. We found that concentrations of 11 proteins varied substantially among hFF samples from single donors and those proteins are promising targets to identify biomarkers useful in oocyte quality assessment.

New AMH assay allows rapid point of care measurements of ovarian reserve

Article

May 2017

In this study, we compare two commercial automated immunoassays used to evaluate serum anti-Müllerian hormone (AMH) levels as a prognostic value for ovarian response and pregnancy outcome in assisted reproductive technology cycles. Serum AMH was measured for 193 women. We performed a simultaneous measurement in serum AMH with the two alternative kits VIDAS® and Elecsys® AMH assay. For all women undergoing in vitro fertilization cycle, we collected data on their antral follicle count (AFC) and numbers of retrieved cumulus oocyte complexes (OC) and metaphase II oocytes and pregnancy outcome. The AMH values provided by VIDAS® were correlated with the values obtained with Elecsys® (0.977 for fresh and 0.971 for the frozen samples). For both assays AMH exhibited a moderate positive correlation with AFC, OC and MII oocytes (0.612, 0.674, 0.605 for VIDAS® and 0.570, 0.617, 0.530 for Elecsys®, respectively). AMH prediction of biochemical and clinical pregnancy was similar. The present results suggest that the VIDAS® AMH assay is broadly comparable to the Elecsys-AMH assay in terms of technical performance for clinical or epidemiological use. Both automated assays performed in a similar way and the choice of assay can be made depending on the technical configuration of each laboratory.

Clinical utility of different anti-Müllerian hormone – AMH assays for the purpose of pregnancy prediction

Article

Apr 2017

Purpose: Comparison of outcomes of IVF cycles where the AMH levels was measured with five different AMH kits: Immunotech (IOT), Beckman Coulter II Gen. RUO, Beckman Coulter II Gen. IVD (BC II IVD), Ansh Labs ultrasensitive (Ansh) and the automated Elecsys Roche assay. Methods: Retrospective analysis of clinical data for 3693 cycles. Results: In women < 35 years with low (<0.6 ng/ml) and high (>1.4 ng/ml) AMH concentrations, and in those > 39 years with medium (≥0.6 and ≤1.4 ng/ml) and high AMH concentrations the clinical pregnancy rate differed significantly among groups of patients whose AMH level was measured with different kits. In those subgroups, the highest rates were recorded for the BC II IVD and Ansh groups, while the lowest in the IOT group. AMH concentrations differed significantly between different kits in all age groups (the highest in each age group was for the IOT kit and the lowest for BC II IVD). AMH correlates positively with antral follicle count, MII and number of oocytes retrieved. Conclusions: This study demonstrated that we could expect very different pregnancy rates with the same AMH results depending on the AMH kit used. That would means, different values of AMH could similarly lead to misleading clinical decisions in IVF.

Journal of Obstetrics and Gynaecology The role of ovarian reserve markers in prediction of clinical pregnancy The role of ovarian reserve markers in prediction of clinical pregnancy

Article

Mar 2017

To evaluate the role of ovarian reserve markers in the prediction of clinical pregnancy and embryo transfer accomplishment among poor responder IVF applicants. 304 female poor responder IVF applicants were included in this prospective cohort study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF outcomes were compared in pregnant and non-pregnant groups as well as in ET vs. non-ET groups. The number of retrieved oocytes was significantly correlated positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH and AFC were similar to the rate of pregnancy. Quartiles of AMH (

Anti-Müllerian hormone: Structure, properties and appliance

Article

Sep 2016
Ginekol Pol

Anti-Mullerian hormone (AMH) is a glycoprotein produced by the granulosa cells of preantral and small antral follicles. AMH concentrations reflect ovarian physiology with high precision, thus serving as a more sensitive marker of the ovarian reserve than the chronological age. This hormone plays a role in the pathogenesis of menstrual disorders and fertility in obesity and polycystic ovary syndrome. The evaluation of AMH may also be useful in the diagnosis or the monitoring therapy of granulosa cells ovarian tumors.

Anti-Müllerian hormone: a critical factor for female fertility and reproductive health

Article

Full-text available

Jul 2016
Ginekol Pol

Anti-Mullerian hormone (AMH) is a glycoprotein produced by the granulosa cells of preantral and small antral follicles. AMH concentrations reflect ovarian physiology with high precision, thus serving as a more sensitive marker of the ovarian reserve than chronological age. This hormone plays a role in the pathogenesis of menstrual disorders and fertility in both obesity and polycystic ovary syndrome. The evaluation of AMH may also be useful in diagnosing or monitoring therapy of granulosa cell ovarian tumors.

Fertility in women of late reproductive age: the role of serum anti-Müllerian hormone (AMH) levels in its assessment

Article

Full-text available

Jun 2016
J ENDOCRINOL INVEST

Introduction: Fertility is referred to the capability for having offspring and can be evaluated by fertility rate. Women's fertility is strictly dependent on individual's age. The fertility peak occurs in the early 20s, and it starts to decline in the third and fourth decades of life (falling sharply after age 35). Aim: The aim of this work is to review the available data concerning fertility in women of late reproductive age, especially the role of serum anti-Müllerian hormone (AMH) levels. Results: There are a lot of factors responsible for decrease of fertility in women of late reproductive age. These factors can be classified as oocyte-dependent (decrease in oocyte quantity and quality) and oocyte-independent (reproductive organs [uterus, oviducts] status and general health). Anti-Müllerian hormone (AMH) is a dimeric glycoprotein of the transforming growth factor-β (TGF-β) superfamily produced directly by the ovarian granulosa cells of secondary, preantral, and early antral follicles. It has been used as an ovarian reserve marker since 2002. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women. Evaluation of AMH's predictive value in the naturally aging population is important for counseling women about reproductive planning as well as for treatment planning for women experiencing hormone-sensitive gynecological conditions such as endometriosis and fibroids. Conclusions: AMH can be considered as an indicator of fertility in late reproductive age women and pregnancy outcome in assisted reproductive technology cycles. AMH can strongly predict poor response in the controlled ovarian stimulation.

Next generation sequencing for preimplantation genetic testing of blastocysts aneuploidies in women of different ages

Article

Full-text available

Dec 2015
ANN AGR ENV MED

Most of the current preimplantation genetic screening of aneuploidies tests are based on the low quality and low density comparative genomic hybridization arrays. The results are based on fewer than 2,700 probes. Our main outcome was the association of aneuploidy rates and the women's age. Between August-December 2013, 198 blastocysts from women (mean age 36.3+-4.6) undergoing in vitro fertilization underwent routine trophectoderm biopsy. NGS was performed on Ion Torrent PGM (Life Technologies). The results were analyzed in five age groups (<31, 31-35, 36-38, 39-40 and >40). 85 blastocysts were normal according to NGS results. The results in the investigated groups were (% of normal blastocyst in each group): <31 (41.9%), 31-35 (47.6%), 36-38 (47.8%), 39-40 (37.7%) and >40 (38.5%). Our study suggests that NGS PGD is applicable for routine preimplantation genetic testing. It allows also for easy customization of the procedure for each individual patient making personalized diagnostics a reality.

Outcome of Assisted Reproduction Treatment in Women with Extremely Low Antimullerian Hormone (AMH) Levels

Article

Full-text available

Jan 2014

Abstract Purpose: To evaluate age related ovarian response to controlled ovarian hyperstimulation, clinical pregnancy and ongoing pregnancy rates beyond 20 weeks in women undergoing assisted reproduction treatment (ART) with antimullerian hormone (AMH) levels of <5 pmol/l. Methods: Retrospective analysis of data from 63 women with AMH of <5 pmol/L who underwent their first assisted reproduction treatment (In-vitro fertilization, IVF and intracytoplasmic sperm injection, ICSI) cycle. Results were analyzed after dividing patients in two groups, group 1 included women of ≤38 years and group 2 > 38 years of age. Non parametric variables were expressed as median (Interquartile range) and compared by Kruskal-Wallis test. Categorical variables were expressed as numbers with proportions (%) and compared by Fisher’s exact test. Results: There was no statistical difference in body max index, level of antimullerian hormone (AMH), follicle stimulating hormone (FSH), dose of gonadotrophins used and cycles cancellation rate in two groups. Although number of oocytes retrieved (median 5), clinical pregnancy (18.4%) and ongoing pregnancy rate beyond 20 weeks (18.4%) was higher in group 1, there was no statistical difference between the two groups. There was one miscarriage in group 2. Conclusion: Women with extremely low-serum AMH levels can still have clinical pregnancy and ongoing pregnancies beyond 20 weeks after ART, though chances will be lower than women with normal ovarian reserve.

An assessment of anti-Müllerian hormone in predicting mating outcomes in female hamsters that have undergone natural and chemically-accelerated reproductive aging

Article

Mar 2015
GEN COMP ENDOCR

In mammals, female fertility declines with age due in part to a progressive loss of ovarian follicles. The rate of follicle decline varies among individuals making it difficult to predict the age of onset of reproductive senescence. Serum anti-Müllerian hormone (AMH) concentrations correlate with the numbers of ovarian follicles, and therefore, AMH could be a useful predictor of female fertility. In women and some production animals, AMH is used to identify which individuals will respond best to ovarian stimulation for assisted reproductive technologies. However, few studies have evaluated AMH's predictive value in unassisted reproduction, and they have yielded conflicting results. To assess the predictive value of AMH in the context of reproductive aging, we prospectively measured serum AMH in 9-month-old Siberian hamsters shortly before breeding them. Female Siberian hamsters experience substantial declines in fertility and fecundity by 9months of age. We also measured serum AMH in 5-month-old females treated with 4-vinylcyclohexene diepoxide (VCD), which selectively destroys ovarian follicles and functionally accelerates ovarian aging. Vehicle-treated 5-month-old females served as controls. AMH concentrations were significantly reduced in VCD-treated females yet many females with low AMH reproduced successfully. On average, both young and old hamsters that littered had higher AMH concentrations than females that did not. However, some females with relatively high AMH concentrations failed to litter, whereas several with low AMH succeeded. Our results suggest that mean AMH concentration can predict mating outcomes on a population or group level, but on an individual basis, a single AMH determination is less informative. Copyright © 2015. Published by Elsevier Inc.

Live Birth Rates in Women Under 38 Years Old with AMH Level

Article

Sep 2022

Many studies failed to show a predictive impact of AMH levels on the chances of pregnancy; however, acceptable pregnancy rates for young women with low AMH levels were observed in IVF + / − ICSI. The objectives of this retrospective study were to evaluate the clinical pregnancy and live birth rates in the first IVF + / − ICSI cycle in women under 38 years old with AMH level < 1.2 ng/ml and to determine the arguments for care. We classified the women into three groups: group A: AMH < 0.4 ng/ml (n: 86); group B: AMH: 0.4 to 0.8 ng/ml (n: 90); and group C: AMH > 0.8 to < 1.2 ng/ml (n: 92). We recorded data on the patients’ characteristics, stimulation cycles, embryo cultures, and ongoing pregnancies. No difference was observed between the three groups for the number of embryos transferred, the clinical pregnancy, and the live birth rates (LBR) per embryo transfer (LBR/transfer: 24.1% in group A, 25.9% in group B, and 28.1% in group C). The young age of the women reassures about the oocyte quality, but a low level of AMH may raise concerns about a lower quantitative oocyte yield, leading to accelerated management of the couple in IVF + / − ICSI.

Ovarian Stimulation in Poor Responders

Chapter

Apr 2022

Ovarian stimulation is the starting point of reproductive medicine but the procedure can result in adverse reactions particularly the dangerous ovarian hyperstimulation syndrome. Fully revised in line with modern practice of ovarian stimulation, this new edition is divided into six sections that cover mild forms, non-conventional forms, IVF, complications and their management, alternatives, and the practicalities of procedures. All aspects of ovarian stimulation are discussed including the different stimulation protocols from which to choose, the management of poor responders and hyper-responders, as well as stimulation in patients with PCOS. Comprehensively reviewing the modern approach to ovarian stimulation, the alternative procedures are also described, both in IVF and other methods of assisted reproduction. Written by leading experts on reproductive health and fertility, this book will assist infertility specialists, gynecologists, reproductive endocrinologists and radiologists in determining successful treatment for their patients.

Anti-müllerian hormone levels are associated with live birth rates in ART, but the predictive ability of anti-müllerian hormone is modest

Article

May 2018
EUR J OBSTET GYN R B

Objectives: The aim was to evaluate the association between serum Anti-Müllerian Hormone (AMH) level and cumulative live birth rates (LBR) in patients undergoing their first in vitro fertilization (IVF) treatment cycle, and to compare serum AMH levels with Antral Follicle Count (AFC) and Ovarian Sensitivity Index (OSI) as predictors of live birth. Study design: A prospective cohort study of 454 patients under the age of 40 and with a regular menstrual cycle of 21-35 days, undergoing their first IVF treatment cycles between September 2010 and June 2015. Participants were divided into three groups based on their AMH level, (AMH ≤10, AMH 10-<30 and AMH ≥30 pmol/l). Any difference in AMH-distribution between patients with or without live birth was analyzed using a Mann-Whitney-test, and live birth rates were compared between groups by a chi-squared test for linear trend. The ability of AMH, OSI and AFC as predictors of live birth was assessed by a receiver operating characteristics-analysis and the area under the curve (AUC) was calculated. Results: Patients with live birth had a higher AMH, median (range) 26 [0-137] pmol/l, compared with patients without live birth, AMH 22 [0-154] pmol/l, p = 0.035. Mean live birth rate (SD) was 0.36 (0.48) in the total cohort, 0.26 (0.44) in AMH-group <10, 0.34 (0.48) in AMH-group 10-<30, and 0.41(0.49) in AMH-group ≥30. Thus live birth rates increased with 8% per AMH-group (95% CI: 0.02 -0.14, p = 0.015). The AUC for AFC was 0.56, for AMH 0.57 and for OSI 0.63, respectively. Conclusion: AMH concentration in serum is associated with live birth rates after IVF. Our results suggest that both AMH, AFC and OSI have an equal but modest predictive ability in relation to live birth rate.

The use of anti-Müllerian hormone (AMH) for controlled ovarian stimulation in assisted reproductive technology and for fertility assessment and -counselling

Article

Feb 2018

Ovarian reserve can be determined by serum anti-Müllerian hormone (AMH) level and/or antral follicle count prior to controlled ovarian stimulation. The aim of controlled ovarian stimulation is to achieve an appropriate number of mature follicles and avoid complications such as ovarian hyperstimulation syndrome. Measurement of the ovarian reserve is very useful for the clinicians as it predicts the ovarian response to controlled ovarian stimulation. Further it assists in giving the patient realistic expectations regarding the treatment. By determining the ovarian reserve, the most appropriate stimulation protocol and gonadotrophin dose can be chosen specifically for each woman enabling the so called 'individualized treatment' in line with the personalized treatment concept. Many benefits come with using AMH as a biomarker for ovarian reserve; the hormone is considered fairly cycle independent apart from a small decrease in the late follicular phase and there is no inter-observer variance. However, the use of AMH also has limitations; since the AMH implementation in fertility treatment several AMH assays have been developed. This has made direct comparisons of AMH serum levels complicated. Currently, no international standardised assays exist. AMH is a valid predictor of the ovarian response to controlled ovarian stimulation and to some extent the chance of pregnancy in relation to assisted reproductive technology, but AMH is less optimal in prediction of spontaneous pregnancy and live birth after assisted reproductive technology. Accordingly, AMH can be used to optimize gonadotrophin stimulation in fertility treatment, but is not recommended as a screening tool in the general population. This article is protected by copyright. All rights reserved.

Successful Spontaneous Conception and Live Birth in a Woman With an Extremely Low Level of Anti-M?llerian Hormone Who Received Korean Herbal Medicine (Bogungsamul-tang): A Case Report

Article

Feb 2017

Conventional treatments do not appreciably improve fecundity in women with extremely low-serum levels of anti-M?llerian hormone (AMH). In Korea, herbal medicine is widely used to treat female infertility. We report a case in which an infertile woman with a very low AMH level naturally conceived after two months of herbal treatment (Bogungsamul-tang), ultimately giving birth to a full-term baby. Although AMH levels were not measured immediately before and after treatment, our study suggests that Korean herbal remedies are a viable option for infertile women with negligible AMH levels. Further studies should be performed to fully assess the clinical effects of Bogungsamul-tang in such women.

Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimüllerian hormone: A multivariate analysis of over 5,000 autologous cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012-2013

Article

Oct 2015

Objective: To assess cycle outcomes when antimüllerian hormone (AMH) is ultralow (≤0.16 ng/mL) and to determine which parameters contribute to the probability of cycle cancellation and/or outcome. Design: Retrospective analysis. Setting: Not applicable. Patient(s): 5,087 (7.3%) fresh and 243 (1.5%) thawed cycles with ultralow AMH values. Intervention(s): Linear and logistic regression, comparison with age-matched cycles with normal AMH concentrations. Main outcome measure(s): Cancellation rate; number of retrieved oocytes, embryos, transferred embryos, and cryopreserved embryos; clinical pregnancy, live-birth, and multiple birth rates. Result(s): The total cancellation rate per cycle start for fresh cycles was 54%. Of these, 38.6% of the cycles were canceled before retrieval, and 3.3% of cycles obtained no oocytes at time of retrieval. Of all retrieval attempts, 50.7% had three oocytes or fewer retrieved, and 25.1% had no embryo transfer. The live-birth rates were 9.5% per cycle start. Cycles with ultralow AMH levels compared with age-matched normal AMH cycles demonstrated more than a fivefold greater preretrieval cancellation rate and a more than twofold less live-birth rate per cycle. Conclusion(s): Refusing treatment solely on the basis of ultralow AMH levels is not advisable, but patients should be counseled appropriately about the prognostic factors for cancellation and outcomes.

Comparison of the second-generation Beckman Coulter IVD and first-generation AnshLabs ELISA assays for anti-Müllerian hormone in patients undergoing IVF treatment

Article

Full-text available

Oct 2014
Ginekol Pol

Objectives: Ovarian reserve is the main factor influencing the efficacy of infertility treatment. Currently the anti- Müllerian hormone is the main indicator of the ovarian reserve and has a wide spectrum of clinical importance. It achieved a high clinical value right after the introduction of the first commercial AMH assays in 2005. Lack further research and development of the tests and monopoly on their production have led to a significant reduction of their quality resulting in lowered veracity and usefulness. Therefore, we searched for an alternative to the Beckman Coulter assay. The objective of the study was to draw a comparison between the commonly used second-generation assay by Beckman Coulter and the ultra-sensitive first-generation assay by AnshLabs. Materials and methods: Serum samples (n=520) were collected from female patients undergoing routine AMH evaluation before entering an IVF program. We chose samples of patients with the lowest correlation between the AMH serum level and response to stimulation. The AMH serum levels of the patients were examined using two AMH tests, the second-generation assay by Beckman Coulter and the first-generation assay by AnshLabs. Precision and accuracy of both methods were determined and the results of AMH serum levels of 130 patients were correlated with the number of: antral follicles (AFC), follicles after stimulation, and the obtained cumulus cells. Results: Both precision and accuracy of the compared methods were highly satisfactory. The coefficients of variation obtained in the study conducted on two different levels of control material were lower than 12% and the load did not exceed 9%. The study proved that both of the methods yielded comparable results. The coefficient of variation between the first-generation and the second-generation AMH assays was 0.871. Conclusion: Both methods might be applied in the evaluation of the ovarian reserve. The first- and second-generation assays show comparable correlation with the clinical effects of stimulation, however it seems that first-generation assays are a better alternative to the unstable second-generation kits. The results from the first-generation assays are distributed on a wider range, which facilitates clinical interpretation.

The impact of endometriosis and its staging on assisted reproduction outcomes: a systematic review and meta-analysis

Article

Sep 2014
ULTRASOUND OBST GYN

Recent progress in the utility of anti-Müllerian hormone in female infertility

Article

Apr 2014
CURR OPIN OBSTET GYN

To discuss the recent developments in the utility of anti-Müllerian hormone (AMH) in the context of female infertility. AMH measurements have entered the clinical practice in counseling of women before in-vitro fertilization (IVF) treatment. AMH measurements can predict both poor and hyperresponse, and can enable clinicians to individualize the treatment strategies. In natural conception, AMH is a good predictor of age at menopause, but it is unclear whether AMH correlates with the fecund ability in the normal population. AMH has also proven its utility in the assessment of ovarian damage due to gonadotoxic treatment or ovarian surgery. Lastly, AMH might assist in the initial diagnosis of oligomenorrhea or amenorrhea, as high levels of AMH are suggestive of polycystic ovarian syndrome and seem to correlate with the severity of the syndrome. AMH is a glycoprotein secreted by the granulosa cells of small growing follicles and indirectly reflects the primordial follicle pool. The ovaries contain a limited number of primordial follicles and their depletion marks the menopause. Thus, the remaining primordial follicle pool is referred to as the ovarian reserve. The clearest data for the clinical utility of AMH is in the context of IVF. The support for other indications is weaker, but rapidly increasing.

Impact of endometriosis and its staging on assisted reproduction outcome: Systematic review and meta-analysis

Article

Sep 2014
ULTRASOUND OBST GYN

Objective Evaluate whether the presence or severity of endometriosis affect the outcomes of assisted reproductive techniques (ART).Methods In this systematic review all studies comparing the ART outcomes of women with and without endometriosis or at different stages of the disease were considered eligible. We used either risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) for comparisons. Our primary outcome was live birth; the secondary outcome was clinical pregnancy. Miscarriage and the number of oocytes retrieved were examined as additional outcomes.ResultsWe included 90 studies in the review and 76 in the meta-analysis: 20,167 women with endometriosis were compared with 121,931 women without endometriosis; and 1,703 women with endometriosis III/IV were compared with 2,227 women with endometriosis I/II. The following results were observed for the comparison women with endometriosis vs. women without endometriosis: live birth, RR=0.99 (95%IC=0.92-1.06); clinical pregnancy, RR=0.95 (95%IC=0.89-1.02); miscarriage, RR=1.31 (95%IC=1.07-1.59); number of oocytes retrieved, MD= − 1.56 (95%IC= − 2.05 to −1.08). The following results were observed for the comparison women with endometriosis III/IV vs. I/II: live birth, RR=0.94 (95%CI=0.80-1.11); clinical pregnancy, RR=0.90 (95%CI=0.82-1.00); miscarriage, RR=0.99 (95%CI=0.73-1.36); number of oocytes retrieved, MD= − 1.03 (95%CI= − 1.67 to −0.39).Conclusions Women with endometriosis undergoing ART have practically the same chance of achieving clinical pregnancy and live birth than women with other causes of infertility. No relevant difference was observed in the chance of achieving clinical pregnancy and live birth following ART when comparing endometriosis III/IV with endometriosis I/II. The quality of the evidence for the additional examined outcomes was very low, not allowing meaningful conclusions.

Anti-Mullerian Hormone (AMH) based prediction model for the live birth in assisted reproductive technology (ART)

Article

Full-text available

Feb 2011

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother-Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.

Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: A randomized prospective study

Article

Full-text available

Oct 2010
HUM REPROD

The aim of this study was to evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on in vitro fertilization (IVF) data and outcomes among poor-responder patients. A randomized, prospective, controlled study was conducted. All patients received the long-protocol IVF. Those in the study group received 75 mg of DHEA once a day before starting the next IVF cycle and during treatment. Thirty-three women with significantly diminished ovarian reserves were enrolled, 17 in the DHEA group and 16 in the control group. The 33 patients underwent 51 IVF cycles. The DHEA group demonstrated a non-significant improvement in estradiol levels on day of hCG (P = 0.09) and improved embryo quality during treatment (P = 0.04) between first and second cycles. Patients in the DHEA group also had a significantly higher live birth rate compared with controls (23.1% versus 4.0%; P = 0.05), respectively. Six of seven deliveries were among patients with secondary infertility (P = 0.006). Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment. Clinicaltrials.gov: NCT01145144.

Impact of female age and male infertility on ovarian reserve markers to predict outcome of assisted reproduction technology cycles

Article

Full-text available

Sep 2009
REPROD BIOL ENDOCRIN

This study was designed to assess the capability of ovarian reserve markers, including baseline FSH levels, baseline anti-Müllerian hormone (AMH) levels, and antral follicle count (AFC), as predictors of live births during IVF cycles, especially for infertile couples with advanced maternal age and/or male factors. A prospective cohort of 336 first IVF/ICSI cycles undergoing a long protocol with GnRH agonist was investigated. Patients with endocrine disorders or unilateral ovaries were excluded. Among the ovarian reserve tests, AMH and age had a greater area under the receiving operating characteristic curve than FSH in predicting live births. Furthermore, AMH and age were the sole predictive factors of live births for women greater than or equal to 35 years of age; while AMH was the major determinant of live births for infertile couples with absence of male factors by multivariate logistic regression analysis. However, all the studied ovarain reserve tests were not preditive of live births for women < 35 years of age or infertile couples with male factors. The serum AMH levels were prognostic for pregnancy outcome for infertile couples with advanced female age or absence of male factors. The predictive capability of ovarian reserve tests is clearly influenced by the etiology of infertility.

Anti-Mullerian hormone-based approach to controlled ovarian stimulation for assisted conception

Article

Full-text available

Feb 2009
HUM REPROD

Individualization of controlled ovarian stimulation (COS) for assisted conception is complicated by variable ovarian response to follicle stimulating hormone. We hypothesized that anti-Müllerian hormone (AMH), a predictor of oocyte yield, may facilitate treatment strategies for women undergoing COS, to optimize safety and clinical pregnancy rates. Prospective cohort study of 538 patients in two centres with differential COS strategies based on a centralized AMH measurement. AMH was associated with oocyte yield after ovarian stimulation in both centres, and a 'reduced' AMH (1 to <5 pmol/l) was associated with a reduced clinical pregnancy rate. Women with a 'normal' AMH (5 to <15 pmol/l) treated with a long GnRH-agonist protocol (both centres) showed a low incidence of excess response (0%) and poor response (0%). In women with 'high' AMH (>15 pmol/l), the antagonist protocol eliminated the need for complete cryopreservation of embryos due to excess response (P < 0.001) and showed a higher fresh cycle clinical pregnancy rate than agonist cycles [OR 4.40 (95% CI 1.95-9.93), P < 0.001]. The use of circulating AMH to individualize treatment strategies for COS may result in reduced clinical risk, optimized treatment burden and maintained pregnancy rates, and is worthy of prospective randomized examination.

Anti-Mullerian Hormone, Inhibin B, and Antral Follicle Count in Young Women with Ovarian Failure

Article

Full-text available

Mar 2009
J CLIN ENDOCR METAB

Ovarian dysfunction is classically categorized on the basis of cycle history, FSH, and estradiol levels. Novel ovarian markers may provide a more direct insight into follicular quantity in hypergonadotropic women. The objective of the study was to investigate the distribution of novel ovarian markers in young hypergonadotropic women as compared with normogonadotropic regularly menstruating women. This was a nationwide prospective cohort study. The study was conducted at 10 hospitals in The Netherlands. Women below age 40 yr with regular menses and normal FSH (controls; n = 83), regular menstrual cycles and elevated FSH [incipient ovarian failure (IOF); n = 68]; oligomenorrhea and elevated FSH [referred to as transitional ovarian failure (TOF); n = 79]; or at least 4 months amenorrhea together with FSH levels exceeding 40 IU/liter [premature ovarian failure (POF); n = 112]. MAIN OUTCOME Measures: Serum levels of anti-Müllerian hormone (AMH), inhibin B, and antral follicle count (AFC) was measured. All POF patients showed AMH levels below the fifth percentile (p(5)) of normoovulatory women. Normal AMH levels (>p(5)) could be identified in 75% of IOF, 33% of TOF patients, and 98% of controls. AFC and AMH levels changed with increasing age (P < 0.0001), whereas inhibin B did not (P = 0.26). AMH levels were significantly different between TOF and IOF over the entire age range, whereas AFC became similar for TOF and IOF at higher ages. Compared with inhibin B and AFC, AMH was more consistently correlated with the clinical degree of follicle pool depletion in young women presenting with elevated FSH levels. AMH may provide a more accurate assessment of the follicle pool in young hypergonadotropic patients, especially in the clinically challenging subgroups of patients with elevated FSH and regular menses (i.e. IOF) and in hypergonadotropic women with cycle disturbances not fulfilling the POF diagnostic criteria (i.e. TOF).

Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain

Article

Full-text available

May 1991
FERTIL STERIL

In a 3-year prospective study of 643 consecutive laparoscopies for infertility, pelvic pain, or infertility and pain, the pelvic area, the depth of infiltration, and the volume of endometriotic lesions were evaluated. The incidence, area, and volume of subtle lesions decreased with age, whereas for typical lesions these parameters and the depth of infiltration increased with age. Deeply infiltrating endometriosis was strongly associated with pelvic pain, women with pain having larger and deeper lesions. Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class, considerations for a simplifying revision with inclusion of deep lesions are suggested. In conclusion, suggestive evidence is presented to support the concept that endometriosis is a progressive disorder, and it is demonstrated that deep endometriosis is strongly associated with pelvic pain.

Follicular hormonal environment and embryo quality in women with endometriosis

Article

Full-text available

Jan 2000

The use of in-vitro fertilization (IVF) as a therapeutic tool in patients with endometriosis has provided information about the disease and, in particular, aspects of the reproductive process in humans, particularly folliculogenesis, fertilization, embryo development and implantation. Retrospective analyses of IVF and oocyte donation programmes showed impaired implantation in patients with endometriosis. Otherwise, the observation that embryo development was blocked more frequently in cases of endometriosis, suggested that impaired embryo quality may be responsible for the reduced implantation rates. Similarly, women with the disease undergoing oocyte donation had the same chance of implantation as patients without endometriosis, suggesting that the endometrial milieu is not affected in patients with endometriosis. The quality of the oocyte may, therefore, be altered in patients with endometriosis. To investigate this, we studied steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and human chorionic gonadotrophin (HCG)-induced granulosa cell cultures. We postulated that the pattern of progesterone secretion may be related to the release of cytokines by ovarian and/or immune cells. To test this, we measured interleukin (IL)-1, IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were increased in natural cycles in women with endometriosis and showed a significant decrease in stimulated cycles in IVF. Also, IL-6 concentrations were increased in the follicular fluid of women with endometriosis and released in higher amounts by granulosa-luteal cells from patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of endometriosis patients. These observations show that the follicular environment is different in cases with endometriosis and suggest that infertility in patients with endometriosis may be related to alterations within the oocyte which, in turn, result in embryos of lower quality, and with a reduced ability to implant.

Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome

Article

Full-text available

Dec 2005

We evaluated basal and dynamic hormonal markers [(FSH, inhibin B, estradiol and anti-Mullerian hormone (AMH)] during the follicular phase and luteal phase of the menstrual cycle and ultrasonic ovarian morphology as predictors of IVF outcome. Fifty-six women, aged <38 years, with normal day 3 FSH levels were included prospectively. Serum estradiol, inhibin B and AMH were measured before and 24 h after administration of 300 IU of recombinant FSH on cycle day 3-4 and during the luteal phase. Ovarian volume and antral follicle count (AFC) were evaluated on cycle day 3-4. The predictive value of oocyte number and pregnancy were assessed using uni- and multivariate analysis. Poor responders (<6 oocytes) had significantly lower luteal AMH levels, while high responders (>20 oocytes) had significantly higher AFC, AMH and luteal stimulated inhibin B and estradiol than normal responders. Multivariate regression analyses showed that the best models for predicting oocyte number included AFC, follicular phase AMH and stimulated inhibin B. Only AMH showed a significant difference between pregnant and non-pregnant women at both cycle phases. In young women (<38 years), AFC or basal AMH and stimulated inhibin B predict ovarian response for IVF. The only predictor for pregnancy is follicular or luteal phase AMH.

Serum anti-M??llerian hormone and FSH: Prediction of live birth and extremes of response in stimulated cycles - Implications for individualization of therapy

Article

Full-text available

Oct 2007

Serum concentrations of anti-Müllerian hormone (AMH) correlate with oocyte yield in assisted reproduction treatment (ART) cycles, however, performance of AMH for prediction of live birth is unknown. A total of 340 first cycle IVF/ICSI patients (median age 34.0 years, inter-quartile range 31.0-37.0 years), had basal plasma AMH and FSH measured and their predictive values for live birth and oocyte yield compared. AMH predicts live birth [contribution to variance (CTV) 3.84%, P < 0.001] and oocyte yield (r = 0.71, P < 0.0001, CTV 7.3%, P < 0.0001). Compared with age and FSH, AMH performs better in prediction of live births [area under receiver operating characteristic curve (AUC) 0.62, 95% CI 0.55-0.68; FSH AUC 0.42, 95% CI 0.35-0.49; age AUC 0.48, 95% CI 0.41-0.55, P = 0.0028] and excessive response to ovarian stimulation (AMH AUC 0.90, 95% CI 0.83-0.96; FSH AUC 0.32, 95% CI 0.23-0.40; age AUC 0.57, 95% CI 0.43-0.71, P < 0.001). AMH prediction of oocyte yield is independent of age (r = -0.28, P < 0.0001, CTV 1.4%, P = 0.006), however, a significant negative interaction (CTV 3.6%, P < 0.0001) exists. AMH demonstrates improved differential distributions for non-, poor, normal and excessive ovarian responses relative to FSH and age. Plasma AMH is a superior predictor of live birth and anticipated oocyte yield compared with FSH and age, facilitating individualization of therapy prior to first ART cycle.

Relevance of Anti-M??llerian hormone measurement in a routine IVF program

Article

Full-text available

Jun 2008
HUM REPROD

Diminished ovarian reserve has become a major cause of infertility. Anti-Mullerian hormone (AMH) seems to be a promising candidate to assess ovarian reserve and predict the response to controlled ovarian hyperstimulation (COH). This prospective study was conducted to evaluate the relevance of AMH in a routine IVF program. Three hundred and sixteen patients were prospectively enrolled to enter their first IVF/ICSI-cycle. Age, FSH-, inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses. A total of 132 oocyte retrievals were performed. A calculated cut-off level < or =1.26 ng/ml AMH alone detected poor responders (< or =4 oocytes) with a sensitivity of 97%, and there was a 98% correct prediction of normal response in COH if levels were above this threshold. With levels <0.5 ng/ml, a correct prediction of very poor response (< or =2 oocytes) was possible in 88% of cases. Levels of AMH > or =0.5 ng/ml were not significantly correlated with clinical pregnancy rates. AMH is a predictor of ovarian response and suitable for screening. Levels < or =1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count. Measurement of AMH supports clinical decisions, but alone it is not a suitable predictor of IVF success.

Anti muellerian hormone serum levels in women with endometriosis: A case-control study

Article

Jan 2009

Anti-Mullerian hormone (AMH) based prediction model for the live birth in assisted reproductive technology (ART)

Article

Jan 2010

Guidelines on the number of embryos transferred: A practice committee report

Article

Jan 2004
FERTIL STERIL

Practice Committee

L’AMH sérique n’a pas de valeur prédictive en fécondation in vitro en cycle naturel modifié : analyse de 342 cycles

Article

May 2011
Fuel Energ Abstr

The objective is to compare the IVF procedures in modified natural cycle outcomes according to serum anti-Mullerian hormone (AMH) levels. We included in this retrospective study 342 patients undergoing their first IVF in modified natural cycle. Patients were regrouped in three groups according to their serum AMH level: group 1 was defined by patients with AMH level < 0.97 ng/mL (<25th percentile), group 2, patients with AMH level between 0.97 ng/mL and 2.60 ng/mL (25–75th percentile), and group 3, patients with AMH level between 2.61 ng/mL and 6.99 ng/mL (>75th percentile). The main outcomes were cancellation rate, embryo transfer rate and clinical pregnancy rate, ongoing pregnancy rate and implantation rate. No difference has been observed on cancellation rate, embryo transfer rate, clinical pregnancy rate and implantation rate. The ongoing pregnancy rate per IVF cycle was respectively: 12.8 ± 3.6% for AMH inferior to 0.97 ng/mL versus 12.5 ± 2.5% for AMH between 0.97 to 2.60 ng/mL and 13.4 ± 4.2% for AMH between 2.61 ng/mL and 6.99 ng/mL. In conclusion, IVF in modified natural cycles procedures should be considered as an option for patients with an altered ovarian reserve defined by a serum AMH inferior to 1 ng/mL. Serum AMH level seems a quantitative marker of the ovary but not a quality factor. Serum AMH level does not seem to be a prognostic factor for ongoing pregnancy rated in IVF modified cycles.

Live birth chances in women with extremely low-serum anti-Mullerian hormone levels

Article

Jul 2011
HUM REPROD

To determine whether women with extremely low-serum anti-Mullerian hormone (AMH) levels (<0.1-0.4 ng/ml) still demonstrate live birth potential with assisted reproduction and whether such potential is age dependent. Between January 2006 and October 2009, 128 consecutive infertility patients with AMH ≤0.4 ng/ml were retrospectively evaluated for pregnancy chances and live birth rates after IVF. Patients presented at a mean (±SD) age of 40.8 ± 4.1 years, with mean (±SD) baseline FSH of 15.7 ± 11.1 mIU/ml and mean (±SD) AMH of 0.2 ± 0.1 ng/ml. One hundred and twenty-eight women underwent a total of 254 IVF cycles. Twenty clinical pregnancies were recorded (7.9% per cycle start [95% confidence interval (CI): 4.9-11.9%]; 15.6% cumulative [CI: 9.8-23.1%]). These pregnancies resulted in 13 live births in 12 women (i.e. 11 singletons and a pair of twins) and 8 patients miscarried. Eight deliveries occurred after the first cycle (6.3% per cycle start) and four after subsequent IVF cycles (3.2%). When evaluated according to female age, 70 women ≤42 years presented with 16 clinical pregnancies that resulted in 10 deliveries (14.3%), while 58 patients >42 years presented with four clinical pregnancies that resulted in 2 deliveries (3.4%), representing a reduced pregnancy chance (P = 0.013) and delivery rate (P = 0.036) versus age ≤42 years. With extremely low-serum AMH levels, moderate, but reasonable pregnancy and live birth rates are still possible. Extremely low AMH levels do not seem to represent an appropriate marker for withholding fertility treatment.

Anti-Müllerian hormone serum levels predict response to controlled ovarian hyperstimulation but not embryo quality or pregnancy outcome in oocyte donation

Article

Jan 2011

The objective of this retrospective cross-sectional study was to evaluate the value of basal serum anti-Müllerian hormone (AMH) levels as a predictor of ovarian response and pregnancy outcome in a donor egg program. The study showed that AMH was superior to other biomarkers of ovarian reserve in predicting low and high response in young women selected as oocyte donors, but that it was not predictive of embryo morphology or pregnancy outcome in the recipient population. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

Anti-Müllerian hormone (AMH) defines, independent of age, low versus good live-birth chances in women with severely diminished ovarian reserve

Article

Dec 2010

Maximal receiver operating characteristic curve inflections, which differentiate between better and poorer delivery chances in women with diminished ovarian reserve (DOR) independent of age, were at anti-Müllerian hormone (AMH) 1.05 ng/mL (improved odds for live birth 4.6 [2.3-9.1), 95% confidence interval; Wald 18.8, df = 1], although live births occurred even with undetectable AMH. Pregnancy wastage was very low at AMH ≤0.04 ng/mL but significantly increased at AMH 0.41-1.05 ng/mL, resulting in similarly low live-birth rates at all AMH levels ≤1.05 ng/mL and significantly improved live-birth rates at AMH ≥1.06 ng/mL.

Anti-Mullerian Hormone serum levels in women with endometriosis: A case-control study

Article

Nov 2009
GYNECOL ENDOCRINOL

To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis. A case-control study Women's General Hospital, Linz, Austria. Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male factor (control group). None. AMH serum level. Mean AMH serum level was significantly lower in the study than in the control group (2.75 + or - 2.0 ng/ml vs. 3.46 + or - 2.30 ng/ml, p < 0.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group (3.28 + or - 1.93 ng/ml vs. 3.44 + or - 2.06 ng/ml; p = 0.61). A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group (2.38 + or - 1.83 ng/ml vs. 3.58 + or - 2.46 ng/ml; p < 0.0001). Lower AMH serum levels and an association with the severity were found in women with endometriosis. Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation (COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH, especially in women with severe endometriosis.

Anti Mullerian Hormone (AMH) as a predictive marker in assisted reproductive technology (ART)

Article

Sep 2009
HUM REPROD UPDATE

In women, anti-Müllerian hormone (AMH) levels may represent the ovarian follicular pool and could be a useful marker of ovarian reserve. The clinical application of AMH measurement has been proposed in the prediction of quantitative and qualitative aspects in assisted reproductive technologies (ART). In men AMH is secreted in both the serum and seminal fluid. Its measurement may be useful in clinical evaluation of the infertile male. The PubMed database was systematically searched for studies published until the end of January 2009, search criteria relevant to AMH, ovarian reserve, ovarian response to gonadotrophin stimulation, spermatogenesis and azoospermia were used. AMH seems to be a better marker in predicting ovarian response to controlled ovarian stimulation than age of the patient, FSH, estradiol and inhibin B. A similar performance for AMH and antral follicular count has been reported. In clinical practice, AMH measurement may be useful in the prediction of poor response and cycle cancellation and also of hyper-response and ovarian hyperstimulation syndrome. In the male, the wide overlap of AMH values between controls and infertile men precludes this hormone from being a useful marker of spermatogenesis. As AMH may permit the identification of both the extremes of ovarian stimulation, a possible role for its measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in ovarian reserve testing. Regarding the role of AMH in the evaluation of infertile men, AMH as single marker of spermatogenesis does not seem to reach a satisfactory clinical utility.

Negligible serum anti-müllerian hormone: pregnancy and birth after a 1-month course of an oral contraceptive, ovarian hyperstimulation, and intracytoplasmic sperm injection

Article

May 2009

To describe a patient with isolated negligible (<0.5 ng/mL or <3.6 pmol/L) anti-müllerian hormone (AMH) levels who underwent intracytoplasmic sperm injection (ICSI) for severe oligoasthenoteratozoospermia, displayed ovarian hyperstimulation after a 1-month course of an oral contraceptive (OC), had a singleton pregnancy and delivered a healthy boy. Case report. Reproductive center at a private hospital. A 34-year-old woman with isolated negligible (<0.5 ng/mL or <3.6 pmol/L) AMH level and poor response to controlled ovarian hyperstimulation (COH) and her 38-year-old partner with severe oligoasthenoteratozoospermia. A 1-month course of an OC, modified minimal stimulation cycle with recombinant FSH, antagonist (cetrorelix) administration to inhibit LH surge, triggered ovulation using 10,000 U of hCG and ICSI. Level of AMH, pregnancy, and birth. Three high quality embryos were obtained and transferred 48 hours after ICSI. Transvaginal ultrasound at 8 weeks' gestation showed a vital singleton pregnancy. The pregnancy continued uncomplicated. The patient gave birth to a healthy boy, weighing 3,280 g, by caesarean section at 39 weeks' gestation. Ovarian hyperstimulation, pregnancy, and birth may occur after a short course of an OC and ICSI in poor responder, normogonadotropic, regularly menstruating young women with isolated negligible AMH.

Circulating basal anti-Müllerian hormone levels as predictors of ovarian response in women undergoing ovarian stimulation for

Article

Oct 2008

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Pathogenic mechanisms in endometriosis-associated infertility

Article

Sep 2008

To review the mechanisms by which endometriosis may affect reproductive function. Review of the English literature from 1986 to 2007 after searching Medline, EMBASE, Cochrane, and BIOSIS, as well as relevant meeting abstracts. Fertility research center and obstetrics and gynecology department in a tertiary care hospital. There is compelling evidence in the literature that endometriosis has detrimental effects on ovarian and tubal function and uterine receptivity, resulting in female infertility. The mechanisms of infertility associated with endometriosis remain controversial and include abnormal folliculogenesis, elevated oxidative stress, altered immune function, and hormonal milieu in the follicular and peritoneal environments, and reduced endometrial receptivity. These factors lead to poor oocyte quality, impaired fertilization, and implantation. Through unraveling the mechanisms by which endometriosis leads to infertility, researchers are sure to find a nonsurgical means to diagnose endometriosis, most likely through serum and peritoneal markers. Cytokines, interleukins, oxidative stress markers, and soluble cellular adhesion molecules all show potential to be used as a reliable marker for diagnosing endometriosis. After analyzing the pathogenic mechanisms of endometriosis, it seems that the future treatment of this entity may include cyclo-oxygenase-2 inhibitors, immunomodulators, or hormonal suppressive therapy to eliminate the need for surgical treatment of endometriosis.

Fecundity and infertility in the United States: Incidence and trends

Article

Sep 1991
FERTIL STERIL

The pathophysiology of endometriosis-associated infertility: Follicular environment and embryo quality

Article

Feb 2000
J Reprod Fertil Suppl

Several retrospective analyses of IVF and oocyte donation programmes, performed to gain clinical knowledge of the factors implicated in the aetiology of endometriosis-associated infertility, have demonstrated that the quality of the embryo is affected in patients with endometriosis. To understand the mechanisms of this alteration, the endocrine, paracrine and autocrine conditions induced during folliculogenesis in women with and without endometriosis were investigated. The first approach was to study ovarian steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and hCG-stimulated granulosa cell cultures. It is proposed that the pattern of progesterone secretion may be related to changes in the release of cytokines by ovarian and white blood cells. Hence, a second trial measured interleukin 1 (IL-1), IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were higher in the natural cycles of women with endometriosis than in women in the control group, and were modulated by ovarian stimulation, decreasing significantly in serum from stimulated cycles. In addition, IL-6 concentrations were higher in the follicular fluid of women with endometriosis than in those in the control group and IL-6 was released in higher amounts by granulosa luteal cells of patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of patients with endometriosis. These observations indicate that infertility in patients with endometriosis may be related to alterations within the follicle which, in turn, result in oocytes and embryos of lower quality, as demonstrated in the IVF programme. In addition, these embryos have a reduced ability to implant, as observed in the oocyte donation model. These alterations may be induced by functional changes in the process of folliculogenesis that affect steroid synthesis, as well as by cytokine release by ovarian and blood cells.

Effect of endometriosis on in vitro fertilization

Article

Jul 2002
FERTIL STERIL

To investigate the IVF outcome for patients with endometriosis. Meta-analysis. Academic research center. A MEDLINE search and review of the literature were performed. Patients were classified by level of endometriosis, and controls were classified according to the indication for IVF. Bivariate analysis and multivariate logistic regression was used to estimate overall effect and control for confounding. Pregnancy rates, fertilization rate, implantation rates, and numbers of oocytes retrieved. Twenty-two published studies were included in the overall analysis. The chance of achieving pregnancy was significantly lower for endometriosis patients (odds ratio, 0.56; 95% confidence interval, 0.44-0.70) when compared with tubal factor controls. Multivariate analysis also demonstrated a decrease in fertilization and implantation rates, and a significant decrease in the number of oocytes retrieved for endometriosis patients. Pregnancy rates for women with severe endometriosis were significantly lower than for women with mild disease (odds ratio, 0.60; 95% confidence interval, 0.42-0.87). Patients with endometriosis-associated infertility undergoing IVF respond with significantly decreased levels of all markers of reproductive process, resulting in a pregnancy rate that is almost one half that of women with other indications for IVF. These data suggest that the effect of endometriosis is not exclusively on the receptivity of the endometrium but also on the development of the oocyte and embryo.

Inhibin B and anti-Mullerian hormone: Markers of ovarian response in IVF/ICSI patients?

Article

Nov 2004

The objective of this study was to investigate whether follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH) and inhibin B could be useful in predicting the ovarian response to gonadotrophin stimulation in assisted reproduction patients who are considered to be poor responders. Prospective study. Fertility unit. Blood samples were collected on day five or six in the early follicular phase of an untreated menstrual cycle. Samples were collected from 69 patients. Serum samples were assayed for FSH, AMH and inhibin B using commercial immunoassay kits. Response to gonadotrophin stimulation and number of eggs collected. Among the 69 patients, 52 patients completed an IVF cycle and 17 patients had to cancel the cycle because of poor ovarian response to gonadotrophin stimulation. Mean FSH levels were significantly higher (P < 0.05) in the cancelled group (10.69 +/- 2.27 mIU/mL) compared with the cycle-completed group (7.89 +/- 0.78 mIU/mL). Mean AMH levels were significantly lower (P < 0.01) in the cancelled group (0.175 +/- 0.04 ng/mL) compared with the cycle-completed group (1.13 +/- 0.2 ng/mL). Mean inhibin B levels were significantly lower (P < 0.001) in the cancelled group (70 +/- 12.79 pg/mL) compared with the completed group (126.9 +/- 8.8 pg/mL). Predictive statistics show that AMH is the best single marker and that the combination of FSH, AMH and inhibin B is modestly better than the single marker. Linear regression analysis in the cycle completed patients shows that although FSH (r= 0.25, P < 0.05) and inhibin B (r= 0.35, P < 0.05) have a significant linear association with the number of eggs collected, AMH has the greatest association (r= 0.69, P < 0.001) with the number of eggs collected among the parameters measured. In this particular group of IVF patients, AMH is the best single marker of ovarian response to gonadotrophin stimulation. The combined markers modestly improved the prediction.

Undetectable serum anti-Mullerian hormone levels and occurrence of ongoing pregnancy

Article

Apr 2008

To discuss, on the basis of the experience of two clinical cases and extensive literature review, the significance of extremely low levels of anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance, in infertile women. Case report. University-based infertility clinic at a medical center in Switzerland. Two women, 29 and 41 years of age and with a 2- and 4-year history of secondary infertility, respectively. Clinical, radiological, and biological investigation of infertility, including repeated measurements of the serum AMH with serial ELISA assays. Levels of AMH and development of ongoing pregnancy. Both women had a spontaneous ongoing pregnancy despite undetectable AMH levels. Although it is helpful for day-to-day management of infertile patients, the predictive value of AMH for the occurrence of a spontaneous ongoing pregnancy has limits.

The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count

Article

Apr 2008

To assess the value of antimullerian hormone (AMH) as a test to predict poor ovarian response and pregnancy occurrence after IVF and to compare it with the performance of the antral follicle count (AFC). A systematic review of existing literature and a meta-analysis were carried out. After a comprehensive search, studies were included if 2 x 2 tables for outcomes poor response and pregnancy in IVF patients in relation to AMH or AFC could be constructed. Academic referral center for tertiary care. Cases indicated for IVF. None. Poor response and nonpregnancy after IVF. A total of 13 studies were found reporting on AMH and 17 on AFC. Because of heterogeneity among studies, calculation of a summary point estimate for sensitivity and specificity was not possible. However, for both tests summary receiver operating characteristic curves for the outcome measures poor response and nonpregnancy could be estimated and compared. The curves for the prediction of poor response indicated no significant difference between the performances of AMH and AFC. For the prediction of nonpregnancy, poor performance for both AMH and AFC was found. In this meta-analysis it was shown that AMH has at least the same level of accuracy and clinical value for the prediction of poor response and nonpregnancy as AFC.

Correlation of anti-M??llerian hormone and baseline follicle-stimulating hormone levels

Article

Jul 2008

To compare how a given level of antimüllerian hormone (AMH) might be used to predict the level of FSH. Retrospective cohort study. Academically affiliated private fertility center. Eighty-one women in preparation for an IVF cycle. None. Levels of FSH and AMH before start of ovulation induction. Serum AMH and log-converted FSH levels were negatively correlated (R(2) = 0.42). The linear regression model for FSH, based on random AMH, was as follows: LnFSH = 2.3 + -0.25 x lnAMH; 95% confidence limits of the coefficient 0.-32 to 0.-18, suggesting that an AMH level of 0.5 ng/mL is predictive of a baseline FSH level of 12.1 mIU/mL (95% confidence interval 11.4-12.7 mIU/mL). These data demonstrate a statistical association between FSH and AMH in assessing ovarian reserve. Using FSH and AMH in combination may improve the evaluation of ovarian reserve. However, it remains to be determined which of these two ovarian function parameters is superior in assessing ovarian reserve with a single test and which test, or combination of tests, will in the future be used in routine infertility evaluations.

Revised American society for reproductive medicine classification of endometriosis: 1996

Jan 1997
817-821

American Society For Reproductive Medicine, 1997. Revised American society for reproductive medicine classification of endometriosis: 1996. Fertil. Steril. 67, 817-821.

Society for Assisted Reproductive Medicine and the American Society for Reproductive Medicine

Jan 2004
FERTIL STERIL
772-774

Practice Committee. Society for Assisted Reproductive Medicine and the American Society for Reproductive Medicine, 2004. Guidelines on the Number of Embryos Transferred: A Practice Committee Report. Fertil. Steril. 82, 772-774.

Probability of live birth in women with extremely low anti-Mullerian hormone concentrations

Abstract

No full-text available

Recommended publications

Surgical diminished ovarian reserve after endometrioma cystectomy versus idiopathic DOR: Comparison...

In vitro fertilization outcomes in women with surgery induced diminished ovarian reserve after endom...