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Anti-Müllerian hormone (AMH) is a dimeric glycoprotein, first recognized due to its action in male sex development. In women, it is synthesized by granulosa cells, pre-antral, and antral follicles; its main function in the ovary appears to be the inhibition of the early steps of folliculogenesis. Measurement of serum AMH made the assessment of ovarian reserve possible for more than 30 years. Its use has been expanded for many clinical implications, including assisted reproductive techniques, menopause, reproductive dysfunctions, the degree of ovarian damage/toxicity, and others. Numerous studies executed in this field concluded that AMH declines with aging; it has a positive correlation with oocyte yield in assisted reproduction; it is upregulated in polycystic ovarian syndrome and decreases in ovarian surgery and cancer therapy. This review aims to highlight the Iraqi experience in the implication of AMH assessment in clinical practice. We reviewed the PubMed database regarding the most recent literature in the assessment of AMH in Iraqi Clinical Practice; studies in polycystic ovarian syndrome (PCOS) patients were excluded. The review results show the importance of AMH assessment in many clinical fields especially for the evaluation of ovarian reserve of an infertile woman either to begin treatment strategists or follow-up patients and oncofertility counseling; yet studies must be encouraged in Iraq about it. [ABSTRACT FROM AUTHOR]

Anti-Müllerian hormone (AMH) is a dimeric glycoprotein, first recognized due to its action in male sex development. In women, it is synthesized by granulosa cells, pre-antral, and antral follicles; its main function in the ovary appears to be the inhibition of the early steps of folliculogenesis. Measurement of serum AMH made the assessment of ovarian reserve possible for more than 30 years. Its use has been expanded for many clinical implications, including assisted reproductive techniques, menopause, reproductive dysfunctions, the degree of ovarian damage/toxicity, and others. Numerous studies executed in this field concluded that AMH declines with aging; it has a positive correlation with oocyte yield in assisted reproduction; it is upregulated in polycystic ovarian syndrome and decreases in ovarian surgery and cancer therapy. This review aims to highlight the Iraqi experience in the implication of AMH assessment in clinical practice. We reviewed the PubMed database regarding the most recent literature in the assessment of AMH in Iraqi Clinical Practice; studies in polycystic ovarian syndrome (PCOS) patients were excluded. The review results show the importance of AMH assessment in many clinical fields especially for the evaluation of ovarian reserve of an infertile woman either to begin treatment strategists or follow-up patients and oncofertility counseling; yet studies must be encouraged in Iraq about it.

The availability of direct-to-consumer (DTC) testing has dramatically increased over the past 2 decades, particularly those targeted at reproduction and fertility. Several ethical concerns exist with regard to DTC tests, including the lack of governmental regulation and consumer protection, standardized laboratory methodology, and clinical validity and actionability. Physicians must familiarize themselves with the pitfalls of DTC tests to best aid patients in interpreting DTC test results and guide them toward evidence-based treatment plans.

To evaluate the role of discordant Day-3 follicle stimulating hormone (FSH) & anti-Müllerian hormone (AMH) levels in predicting pregnancy outcome after controlled ovarian stimulation (COS) followed by intrauterine insemination or timed intercourse. Retrospective study of 745 couples with regular menstrual cycles, at least one patent fallopian tube, and normal semen analysis that underwent infertility treatment between June 2013 and March 2017. Women with documented serum AMH and FSH levels (<10 (mIU/ml were considered normal), and undergo COS were studied. Clinical pregnancy rate is the cumulative pregnancy obtained after maximum of three cycles of COS with or without IUI. As expected, patients with normal concordant AMH/FSH achieved a significantly (p <.01) higher pregnancy than all other groups. 22.4% of those with discordant normal AMH/abnormal FSH became pregnant while only 10.8% of those with discordant abnormal AMH/normal FSH levels did. 11.7% of patients with abnormal concordant values achieved pregnancy. Patients with discordant abnormal AMH/normal FSH were not statistically different (p =.084) from abnormal concordance AMH/FSH but significantly (p <.01) lower than normal concordant AMH/FSH. However, patients with discordant normal AMH/abnormal FSH were statistically different from both concordant normal and concordant abnormal AMH/FSH values (p <.04). This study showed that both discordant abnormal Day-3 FSH and/or abnormal AMH serum levels, as well as concordant abnormal FSH and AMH values, were predictive of lower clinical pregnancy rates after COS. However, abnormal FSH with a normal AMH does not have as poor a prognosis as the presence of an abnormal AMH [ABSTRACT FROM AUTHOR]

Several biomarkers of ovarian reserve have been proposed as possible predictors of the response to controlled ovarian stimulation (COS). We aimed to evaluate age, FSH, AMH, antral follicle count (AFC), and ovarian response prediction index (ORPI), as potential predictors of response to COS. Cross-sectional study enrolling of 188 infertile women who underwent the first cycle of IVF/ICSI. AFC was evaluated; serum FSH and AMH levels were measured by ELISA. ORPI was calculated as AMH x AFC/patient´s age. As expected, hypo-responder group had less retrieved oocytes, MII, and embryos compared to the good responders. The hyper-response patients were younger, with lower FSH, increased AMH, AFC, and ORPI values. Regarding the assessment of the predictive capacity of ovarian reserve tests, none of them individually or combined showed a good predictive capacity for hypo-response. With respect to the hyper-responder group, individually AMH was the best predictor, while in the multivariable model, ORPI demonstrated the best predictive capacity. Furthermore, patients with serum AMH < 2.09 ng/mL (p25) had fewer AFC than patients with higher AMH values. Our findings suggest that none of the ovarian reserve tests showed a good predictive capacity for hypo-response, while the ORPI was the strongest predictor of hyper-response in normovulatory infertile women. [ABSTRACT FROM AUTHOR]

The art of ovarian stimulation for IVF/ICSI treatment using exogenous FSH should be balanced against the relative contribution of other steps of the ART process such as the IVF-lab-phase and the Embryo-Transfer. The aim of ovarian stimulation is to obtain a certain number of oocytes, that will enable the best probability of achieving a live birth. It has been suggested that more oocytes will create a better prospect for pregnancy, but studies on the question whether the retrieval of a few oocytes less or more will make the difference are not clearly supportive for this mantra. Personalization strategies have been the subject of many studies over the past 20 years. Creating the optimal response in a patient in terms of live birth prognosis as well as OHSS risks may be based on information from the Ovarian Reserve testing using the Antral Follicle Count or Anti-Mullerian Hormone, the patient's bodyweight, the ovarian response in a previous cycle, and the dosage level of FSH. Taken together, steering the ovarian response into a supposed optimal range may appear difficult as the interrelation for each of these factors with the egg number is weak. Using OR testing for choosing FSH dosage, compared to a standard normal dosage of 150 IU, has been studied in several trials. Dosage individualization, in general, does not appear to improve the prospects for live birth, but the reduction in OHSS risk may be substantial. This implies that the use of high dosages of FSH in predicted LOW responders lacks any cost-benefit for the patient and may be abandoned, while in predicted HIGH responders, reduction of the usual dosage level of 150 IU may create better safety, provided that in case of an unexpected LOW response cancelation of the cycle is refrained from. In view of recent developments in using GnRH agonist triggering of final oocyte maturation, the trend could be that with the Antagonist co-medication system and a standard dosage of 150 IU of FSH, prior ovarian reserve testing may become futile, as safety can be managed well in actual HIGH responders by replacing the high dose hCG trigger.

The demographic shift currently being observed across many Western countries towards older-parenthood has contributed to increasing concerns about the risks posed by age-related fertility decline, particularly in women. These concerns pertain to the increased risk of infertility, pregnancy loss, and genetic abnormalities occurring in the foetus as well as greater physical risks to the potential mother during pregnancy and birth. Concerns about the effects of reproductive ageing have occurred alongside the emergence of variety of 'fertility monitoring' and 'fertility extension' technologies (FMETs) such as ovarian reserve testing and social egg freezing. In this paper I will explore the emergence of these new FMETs and will demonstrate how these new technologies are part of, and are contributing towards, a shift in the way reproductive ageing is perceived and represented, not as a natural inevitability but as a pathological liability in need of monitoring and management. I will show how, by rendering fertility risk 'visible', new and highly gendered anxieties are emerging creating new burdens and responsibilities on women to consider drawing upon highly commercialised biomedical interventions in the pursuit of biogenetic motherhood. I will also examine how, in the current neoliberal moment, these fertility risk individualising technologies can be experienced as highly compelling for potential users due to the ways in which they offer women the opportunity to achieve the goals of hegemonic femininity whilst demonstrating ideals associated with reproductive citizenship. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) is a clinically challenging scenario for patients and providers since an evidence-based approach to evaluation results in no explanation at least 50% of the time. The most common cause of first trimester clinical miscarriage is chromosome imbalance in the embryo or aneuploidy and the incidence of aneuploidy increases with age and diminished ovarian reserve (DOR). Currently, no professional societies recommend ovarian reserve testing in RPL patients, but some research shows a higher rate of DOR in miscarriage patients. The objective of this study was to evaluate the prevalence of DOR in unexplained vs. explained RPL patients. A prospective cohort study was completed, including 264 patients with recurrent pregnancy loss, 87 with an identifiable cause and 177 patients unexplained. A higher percentage of patients with unexplained RPL had DOR compared to patients with a known cause for RPL (48% vs 29%, p =.005). This finding was most significant in patients less than 38 years old compared to patients 38 years old and older (22% vs. 12%, p =.04). In conclusion, DOR is associated with RPL in many patients with otherwise unexplained RPL. Providers should consider adding ovarian reserve testing to their evaluation of RPL patients to guide counseling for treatment options. [ABSTRACT FROM AUTHOR]

There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms. [ABSTRACT FROM AUTHOR]

Antral follicle count (AFC) variation was examined across the menstural cycle and its effect on clinical management assessed. In 79 women, AFC was documented in early (iAFC) and late follicular phase (sAFC). Absolute agreement between iAFC and sAFC and agreement for classification into categories of risk of extremes of ovarian response were examined. Ovarian stimulation protocols designed with iAFC and sAFC, and the predictive value of iAFC and sAFC for extremes of ovarian response, were compared in women undergoing ovarian stimulation. Significant differences were found between iAFC and sAFC (16 [IQR 9–24] versus 13 [IQR 7– 21]; P = 0.001), with moderate agreement for the classification into at risk of extremes of response (k = 0.525). Agreement for protocol selection based on either AFC (k = 0.750) and starting gonadotrophin dose was good (concordance correlation coefficient 0.970 [95% CI 0.951 to 0.982]). Predictive value for iAFC and sAFC was maintained for poor ovarian response and risk of ovarian hyperstimulation syndrome (OR 0.634 [0.427 to 0.920], 0.467 [0.233 to 0.935]) and (OR 1.049 [0.974 to 1.131], 1.140 [1.011 to 1.285]). Across the cycle, AFC varies but does not significantly affect ovarian stimulation protocol design and prediction of extreme ovarian response. [ABSTRACT FROM AUTHOR]

BACKGROUND In women, anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells of ovarian follicles during the early stages of follicle development. After an initial increase until early adulthood, AMH concentrations slowly decrease with increasing age until becoming undetectable ∼5 years before menopause when the stock of primordial follicles is exhausted. However, major individual variability exists in the pace of follicle pool depletion and the initial size of the follicle pool, reflected by a wide range of age at menopause. Individual AMH serum concentration does accurately reflect the size of the pool of antral follicles, representing the quantity of the remaining primordial follicles. Accordingly, AMH levels may vary significantly in women of the same chronological age, allowing AMH to predict the remaining length of a woman's reproductive lifespan. METHODS Following 10 years of intense clinical research in this area (with over 300 papers published in core clinical journals every year), the level of evidence justifying use of AMH in ovarian reserve testing is rapidly increasing. We have conducted a summarizing review regarding all evidence published. RESULTS Many studies have convincingly demonstrated that AMH is the best currently available measure of ovarian reserve under a variety of clinical situations, such as infertility treatment (especially IVF), the forecasting of reproductive lifespan, ovarian dysfunction (especially polycystic ovary syndrome) and gonadotoxic cancer treatment or ovarian surgery. Moreover, AMH may help to individualize dosing for ovarian stimulation thereby improving the efficiency and safety of IVF. However, there are concerns about the performance of the AMH assay under different conditions regarding storage of samples and handling techniques. Therefore an international guideline for laboratories and a reference preparation are needed to make test results between laboratories truly comparable. CONCLUSIONS AMH is the best current available measure of ovarian reserve for different clinical conditions. However, prospective well powered studies comparing different infertility treatment strategies based on initial AMH levels using appropriate end-points, such as live birth and cost-effectiveness, are urgently awaited. Such studies could represent a true step forward in rendering counseling and infertility care more patient tailored. [ABSTRACT FROM AUTHOR]

Objective: To compare how a given level of antimüllerian hormone (AMH) might be used to predict the level of FSH. Design: Retrospective cohort study. Setting: Academically affiliated private fertility center. Patient(s): Eighty-one women in preparation for an IVF cycle. Intervention(s): None. Main Outcome Measure(s): Levels of FSH and AMH before start of ovulation induction. Result(s): 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 × 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). Conclusion(s): 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. [Copyright &y& Elsevier]

Objective: To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population. Design: Retrospective clinical study. Setting: University hospital. Patient(s): General IVF patient population. Intervention(s): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. Main outcome measure(s): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. Result(s): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. Conclusion(s): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates. [Copyright &y& Elsevier]

The availability of direct-to-consumer (DTC) testing has dramatically increased over the past 2 decades, particularly those targeted at reproduction and fertility. Several ethical concerns exist with regard to DTC tests, including the lack of governmental regulation and consumer protection, standardized laboratory methodology, and clinical validity and actionability. Physicians must familiarize themselves with the pitfalls of DTC tests to best aid patients in interpreting DTC test results and guide them toward evidence-based treatment plans., (© 2022 Published by Elsevier Inc. on behalf of American Society for Reproductive Medicine.)

The objective of the study was to compare a standard clomiphene citrate challenge test with inhibin-B serum concentrations also obtained on cycle days 3 and 10 as a negative predictor of pregnancy in a group of 106 women at risk for compromised ovarian function. Mean duration of follow-up was 8.25 months in 95 patients with 30 pregnancies recorded (plus one biochemical). Inhibin-B concentrations on cycle days 3 and 10 were correlated only with each other and not with serum oestradiol, follicle stimulating hormone (FSH) and/or pregnancy rates. Pregnancy occurred in 34.5% (10/29) of all patients with inhibin-B values ≥45 pg/ml on cycle day 3 and in 31.8% (21/66) of those with values <45 pg/ml. For FSH >11 mIU/ml on either day, pregnancy rate was 13.6% versus 38.4% for FSH of ≤9 mIU/ml (P = 0.03). This study reconfirmed the usefulness of a clomiphene citrate challenge test as an indication of ovarian reserve but failed to find clinical value for inhibin-B testing. [ABSTRACT FROM PUBLISHER]

Women are increasingly delaying conception to later years. Hormonal contraception induces artificial cyclicity, which does not, like natural cyclicity, reflect normal, physiological ovarian behaviour. Therefore, long-term users of hormonal contraceptives, in particular, fail to derive potential diagnostic benefits from changes in menstrual cyclicity, which usually alerts patients and physicians to developing ovarian pathology. Timely diagnosis of ovarian problems is further hampered, as anti-Müllerian hormone is suppressed by hormonal contraceptives, making the accurate assessment of functional ovarian reserve more difficult. Women on long-term hormonal contraceptives who develop premature ovarian senescence at young ages, therefore, often go undiagnosed until termination of hormonal contraception, when they present with either post-contraception amenorrhea, other menstrual abnormalities or infertility. As evolving screening options now permit the detection of young women at risk for premature ovarian senescence, it is proposed that young women are offered 'risk screening' for premature ovarian senescence before starting long-term hormonal contraception. A potential protocol is outlined. [ABSTRACT FROM AUTHOR]

The art of ovarian stimulation for IVF/ICSI treatment using exogenous FSH should be balanced against the relative contribution of other steps of the ART process such as the IVF-lab-phase and the Embryo-Transfer. The aim of ovarian stimulation is to obtain a certain number of oocytes, that will enable the best probability of achieving a live birth. It has been suggested that more oocytes will create a better prospect for pregnancy, but studies on the question whether the retrieval of a few oocytes less or more will make the difference are not clearly supportive for this mantra. Personalization strategies have been the subject of many studies over the past 20 years. Creating the optimal response in a patient in terms of live birth prognosis as well as OHSS risks may be based on information from the Ovarian Reserve testing using the Antral Follicle Count or Anti-Mullerian Hormone, the patient's bodyweight, the ovarian response in a previous cycle, and the dosage level of FSH. Taken together, steering the ovarian response into a supposed optimal range may appear difficult as the interrelation for each of these factors with the egg number is weak. Using OR testing for choosing FSH dosage, compared to a standard normal dosage of 150 IU, has been studied in several trials. Dosage individualization, in general, does not appear to improve the prospects for live birth, but the reduction in OHSS risk may be substantial. This implies that the use of high dosages of FSH in predicted LOW responders lacks any cost-benefit for the patient and may be abandoned, while in predicted HIGH responders, reduction of the usual dosage level of 150 IU may create better safety, provided that in case of an unexpected LOW response cancelation of the cycle is refrained from. In view of recent developments in using GnRH agonist triggering of final oocyte maturation, the trend could be that with the Antagonist co-medication system and a standard dosage of 150 IU of FSH, prior ovarian reserve testing may become futile, as safety can be managed well in actual HIGH responders by replacing the high dose hCG trigger.

Protection of fertility shares many of the same concepts as optimization of general health, such as smoking cessation, maintenance of a healthy body weight, and moderation of alcohol intake. Increasing attention has been placed on minimizing exposures to known reproductive toxicants. There are few conclusive data to support specific diet patterns or supplements for fertility. Ovarian reserve testing has been explored as potential diagnostic tests for assessment of reproductive aging with some controversy. Finally, the development of vitrification in the assisted reproduction laboratory has increased the success and, therefore, access to fertility preservation by way of oocyte or embryo cryopreservation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Multiple endocrine, ultrasound‐based and dynamic tests have been proposed for the assessment of ovarian reserve. Lately, ovarian biopsy has been proposed as a more representative functional test of ovarian reserve, and has been recommended as an early step in the investigation of infertility. Central to this hypothesis is the idea that a random biopsy of the ovarian cortex is reflective of the actual ovarian follicular pool. Recent studies have shown a wide variation in the number and distribution of ovarian follicles even from the same ovary and in the same patient. Coupled with the invasiveness of performing the biopsy and the risk of adhesion formation, we believe that there should not be a role for ovarian biopsy in ovarian reserve testing. [ABSTRACT FROM AUTHOR]

Educating couples about natural means to improve fertility should include a discussion about appropriate timing to initiate a diagnostic evaluation for infertility. Complete infertility testing for both male and female factors allows directed care for all abnormalities to optimize chances for conception., (Copyright © 2015 Elsevier Inc. All rights reserved.)