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.

Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss.

STUDY QUESTION: In an intent to treat analysis, are clinical outcomes improved in recurrent pregnancy loss (RPL) patients undergoing IVF and preimplantation genetic screening (PGS) compared with patients who are expectantly managed (EM)? SUMMARY ANSWER: Among all attempts at PGS or EM among RPL patients, clinical outcomes including pregnancy rate, live birth (LB) rate and clinical miscarriage (CM) rate were similar. WHAT IS KNOWN ALREADY: The standard of care for management of patients with RPL is EM. Due to the prevalence of aneuploidy in CM, PGS has been proposed as an alternate strategy for reducing CM rates and improving LB rates. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 300 RPL patients treated between 2009 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among two academic fertility centers, 112 RPL patients desired PGS and 188 patients chose EM. Main outcomes measured were pregnancy rate and LB per attempt and CM rate per pregnancy. One attempt was defined as an IVF cycle followed by a fresh embryo transfer or a frozen embryo transfer (PGS group) and 6 months trying to conceive (EM group). MAIN RESULTS AND THE ROLE OF CHANCE: In the IVF group, 168 retrievals were performed and 38 cycles canceled their planned PGS. Cycles in which PGS was intended but cancelled had a significantly lower LB rate (15 versus 36%, P = 0.01) and higher CM rate (50 versus 14%, P < 0.01) compared with cycles that completed PGS despite similar maternal ages. Of the 130 completed PGS cycles, 74% (n = 96) yielded at least one euploid embryo. Clinical pregnancy rate per euploid embryo transfer was 72% and LB rate per euploid embryo transfer was 57%. Among all attempts at PGS or EM, clinical outcomes were similar. Median time to pregnancy was 6.5 months in the PGS group and 3.0 months in the EM group. LIMITATIONS, REASONS FOR CAUTION: The largest limitation is the retrospective study design, in which patients who elected for IVF/PGS may have had different clinical prognoses than patients who elected for expectant management. In addition, the definition of one attempt at conception for PGS and EM groups was different between the groups and can introduce potential confounders. For example, it was not confirmed that patients in the EM group were trying to conceive for each month of the 6-month period. WIDER IMPLICATIONS OF THE FINDING: Success rates with PGS are limited by the high incidence of cycles that intend but cancel PGS or cycles that do not reach transfer. Counseling RPL patients on their treatment options should include not only success rates with PGS per euploid embryo transferred, but also LB rate per initiated PGS cycle. Furthermore, patients who express an urgency to conceive should be counseled that PGS may not accelerate time to conception. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLLMENT: N/A.

Higher rates of aneuploidy in blastocysts and higher risk of no embryo transfer in recurrent pregnancy loss patients with diminished ovarian reserve undergoing in vitro fertilization.

OBJECTIVE: To study the prediction of aneuploidy rate in blastocysts from patients with recurrent pregnancy loss (RPL) on the basis of ovarian reserve testing. DESIGN: Prospective cohort analysis. SETTING: Private, university-affiliated fertility clinic. PATIENT(S): A total of 239 patients with RPL, defined as two or more clinical miscarriages, were screened for inclusion. One hundred two (102) cycles in patients with unexplained RPL resulted in at least one euploid embryo transferred. Outcomes were compared by ovarian reserve test results, with diminished ovarian reserve (DOR) defined as a cycle day 3 FSH >10 IU/mL and/or antimüllerian hormone <1 ng/mL. INTERVENTION(S): In vitro fertilization with blastocyst biopsy and aneuploidy screening of all 23 chromosome pairs. MAIN OUTCOME MEASURE(S): Rate of aneuploidy in blastocysts and incidence of IVF cycles with no transfer owing to no euploid blasts. RESULT(S): Patients with DOR had a higher percentage of aneuploid blastocysts (57% vs 49%) and a higher incidence of no euploid embryos to transfer (25% vs 13%). The higher rate of aneuploidy in blastocysts was most significant in patients aged <38 years (67% vs 53%). Implantation rates after transfer of euploid blastocysts were similar (61% compared with 59%), and miscarriage rates were low (14% and 10%). CONCLUSION(S): Unexplained RPL patients with DOR have a higher percentage of aneuploid blastocysts and risk of no euploid embryo to transfer compared with unexplained RPL patients with normal ovarian reserve testing. The difference is most significant in patients aged <38 years. Patients with RPL and DOR with euploid embryo transferred had similar outcomes compared with patients with RPL and normal ovarian reserve testing.

Precision of progesterone measurements with the use of automated immunoassay analyzers and the impact on clinical decisions for in vitro fertilization.

OBJECTIVE: To compare the precision of progesterone measurements obtained with the use of immunoassays and of liquid chromatography-tandem mass spectrometry (LC-MS/MS). DESIGN: Comparative study. SETTING: Academic, private practice, and in vitro fertilization (IVF) research centers. PATIENT(S): A total of 189 human serum samples were collected during controlled ovarian hyperstimulation and early pregnancy in women undergoing IVF. INTERVENTION(S): Serum progesterone pools (n = 10; 0.2-4 ng/mL) were sent to four laboratory centers that used four different automated immunoassay analyzers. Progesterone was measured by immunoassay in triplicate at three separate time points (n = 9 per pool) and by LC-MS/MS in triplicate once (n = 3 per pool). MAIN OUTCOME MEASURE(S): Inter- and intraassay coefficients of variation (CVs) of progesterone measurements were compared for each analyzer and LC-MS/MS. RESULT(S): Progesterone measurements by immunoassay were highly correlated with those by LC-MS/MS. Only two analyzers had intraassay CVs <10% at all three experimental time points, and only two analyzers had an interassay CV <10%. Mean progesterone levels by the analyzers were different across multiple progesterone pools. CONCLUSION(S): Our results indicate that progesterone threshold measurements used for IVF clinical decisions should be interpreted cautiously and based on laboratory- and method-specific data. A validated progesterone standard incorporated into daily immunoassays could improve medical decision accuracy.

The diagnosis and reproductive outcome after surgical treatment of the complete septate uterus, duplicated cervix and vaginal septum.

OBJECTIVE: This study was undertaken to evaluate the diagnostic management and the reproductive outcome after surgical repair of a rare reproductive malformation. STUDY DESIGN: Sixteen women with a complete septate uterus, double cervix, and a longitudinal vaginal septum were referred for evaluation. Presenting complaints were chiefly pregnancy loss in parous women (n=9) and dyspareunia in nulligravid women (n=7). The combination of hysterosalpingography, ultrasonography, and/or magnetic resonance imaging was used to correctly identify the anomaly in 15 of the 16 cases. Both hysteroscopic (n=11) and transabdominal (n=5) surgical techniques were used to repair the uterine septum. RESULTS: In no case was the correct diagnosis made before referral; the uterus didelphys was the most common misdiagnosis. The preoperative pregnancy loss was 81%. Postoperatively, 12 women conceived for a total of 17 pregnancies; there were 14 term live births or ongoing pregnancies in the third trimester (82%), with a first trimester spontaneous abortion rate of 18%. In 9 women who conceived after hysteroscopic surgery, term live births occurred in 9 of 12 (75%) conceptions. A modified Tompkins metroplasty was performed in 5 women with subsequent term live births or ongoing third trimester pregnancies in 5 of 5 (100%) patients. CONCLUSION: The identification of a duplicated cervix and a vaginal septum is consistent with several uterine malformations, which leads to frequent misdiagnosis and errors in management. Significant pregnancy wastage, obstetric complications, and dyspareunia are common, and surgical treatment is therefore advisable. Making the best choice between hysteroscopic or transabdominal metroplasty depends on the anatomic features of the cervix and the uterine cavity, but optimal patient management requires familiarity with both techniques.