Validation study of the Access antimüllerian hormone assay for the prediction of poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma. DESIGN: Prospective cohort study. SETTING: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). PATIENT(S): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. RESULT(S): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4). CONCLUSION(S): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible.

High incidence of diminished ovarian reserve in young unexplained recurrent pregnancy loss patients.

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.

Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation.

OBJECTIVE: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved. DESIGN: Prospective cohort study. SETTING: Thirteen private and academic fertility centers in the United States. PATIENTS(S): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15. RESULT(S): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%. CONCLUSION(S): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes.

Acupuncture performed before and after embryo transfer: a randomized controlled trial.

OBJECTIVE: To compare the clinical pregnancy rates in women who underwent fresh embryo transfer (ET) with and without one acupuncture session before and after the transfer using a modified Paulus protocol. STUDY DESIGN: The prospective, physician-blinded study randomized 113 women to either no intervention (n = 56) or acupuncture performed off-site (n = 57). Secondary outcomes were positive pregnancy test and live birth rates. Intent-to-treat analysis and per protocol analysis were performed. RESULTS: No difference in age and in vitro fertilization-embryo transfer (IVF-ET) parameters were detected. Compared to the control group, the treatment group had a lower pregnancy rate (43.6% vs. 64.8%, p = 0.045). More women in the control group had live births than did those in the acupuncture group (56.0% vs. 36.0%, respectively, p = 0.033). Generalized mixed models revealed that patients who received acupuncture had lower odds of clinical pregnancy than those who did not undergo acupuncture treatment (OR = 0.42, 95% CI 0.19-0.93). CONCLUSION: Our study found that acupuncture performed off-site on the day of ET was detrimental to the success of the transfer. More research is needed with a greater number of subjects to elucidate the role of acupuncture before and after ET, ideal treatment frequency, and to further explore the role of individualized acupuncture treatment on IVF-ET pregnancy rates.

Ethical and legal issues in the use of related donors for therapeutic insemination.

Donor insemination involving family members can be complex. Although it may offer some advantages to the requesting individuals, to the donor, or to the family, related donation does raise a significant number of concerns. The specific circumstances of these requests should be considered carefully--in most cases more carefully than with anonymous sperm donation. Still, in the United States the freedom of couples or individuals to decide whether, when, and how to reproduce is highly valued. Respect for the autonomy of the involved family members would favor serious consideration of proposals for intrafamilial sperm donation, when all parties have freely consented to participate. Without exception, standards governing anonymous sperm donation should be followed in evaluating the proposed sperm donor for infectious and genetic diseases. The semen specimens should be frozen and quarantined for 180 days. In many cases, the 6-month delay that results from this quarantine will discourage a couple from pursuing intrafamilial sperm donation. Adequate time is essential to assess these relationships when requested. Multiple visits to physicians, nurses, counselors, and lawyers may be necessary for a thorough assessment. Programs should require prospective participants, including recipients, donors, and partners of donors, to undergo psychologic counseling by a professional knowledgeable about gamete donation. Counselors should address issues such as emotional risks, potential impact on family relationships, the donor-recipient relationship, the future role of the donor in the offspring's life, and what information will be disclosed to the offspring. The process of obtaining informed consent from the requesting individuals, the donor, and, possibly, the donor's wife should involve a thorough discussion of potential risks to all parties. Clinicians should assure that the decision to be a sperm donor has been voulntary and free from manipulative and coercive influences. Financial incentives, including direct and indirect payment and inheritance, should not be so substantial that they become inducements that may lead the prospective donor to discount the emotional risk associated with the procedure. Legal counsel should be strongly encouraged to clarify issues of disclosure, rights, and duties, as well as the donor's relationship to the resulting offspring. Any possible changes in these issues in the event of divorce or death of requesting individuals should be addressed. In certain cases, requests should be immediately denied. Gametes from consanguineous relationships should never be used to initiate a pregnancy. Because of potential parental conflicts of interest, programs should not allow minors under the age of 18 years to donate sperm. The use of a family member may not be appropriate when sperm donation is chosen to prevent genetic diseases. Careful genetic counseling should be done before intrafamilial sperm donation is allowed in this situation. If, after careful consideration of the proposed arrangement, the physician chooses to facilitate the relationship, then all precautions should be taken to prevent medical, psychologic, and legal harm to the requesting couple or individual, the potential donor, and the prospective child. Programs that offer these arrangements should make every effort to obtain long-term follow up on the outcomes of these relationships, so that programs can provide more accurate information to families considering these relationships in the future. The physician or program should not feel obligated to agree to every request for intrafamilial sperm donation. When the assessment reveals consistent concerns about coercion of the prospective donor or about unhealthy family dynamics, the physician should feel free to deny these procedures. The physician should advise the requesting couple or individual to seek alternative methods, such as anonymous sperm donation, to conceive.