Objective: Assisted reproductive technology is used for patients with infertility who also have recurrent pregnancy loss. Recent studies have linked the clomiphene citrate challenge test (CCCT) results with pregnancy loss and the day 3 FSH value with aneuploidy in the abortus. Embryo cleavage rates also correlate with aneuploidy. We sought to assess the embryo quality and clinical outcomes of patients with recurrent pregnancy loss undergoing in vitro fertilization (IVF) by controlling for these potential predictors of aneuploidy. Design: Retrospective case-control study involving review of 3,475 cycles performed January, 1998 and December, 2000. Materials/Methods: Thirty women with the diagnosis of recurrent pregnancy loss and subfertility who had undergone a CCCT subsequently underwent 46 cycles of IVF (median number of losses = 3.1, range 2–6). The majority of the RPL group had no identifiable etiologies (53.0%), 16.6% had correction of uterine cavity abnormalities, 26.6% had a potential immunologic cause, and 10.0% had luteal phase insufficiency. Women with tubal factor infertility served as controls and were matched for age, CCCT results (day 3 and day 10 FSH), total number of embryos and date of retrieval. Outcome measures included ongoing clinical pregnancy rate, early pregnancy loss rate, and embryo quality as assessed by percentage of embryo ≥8-cells. Embryos were further stratified by fragmentation score (<10%, 10–25%, >25%). Data were analyzed using Chi square with the Yates correction or Mann Whitney U with p < 0.05 considered significant. Results: The cumulative pregnancy rate following IVF in the RPL group was 46.6%. The control and RPL groups had similar ongoing pregnancy rates per cycle start (23.9% vs 32.6%, p = 0.35) and pregnancy loss rates (25.0% vs. 44.4%, p = 0.33). The rate of cell cleavage on day 3 did not differ between the control and RPL groups, as indicated by the percentage of ≤4-cell (17.5% vs 23.7%, p = 0.22), 5- to 7-cell (40.4% vs 40.8%, p = 0.92), and ≥8-cell (42.1 vs 35.5, p = 0.66) embryos. Stratification by age also failed to demonstrate a difference in cleavage rate or embryo quality between the RPL and control groups. Patient group characteristics and cycle outcome parameters are summarized in the following table. Cycle parameters and embryo characteristics. Tabled 1ControlRPLp value# Cycles4646Age38.6 ± 2.638.5 ± 2.70.89Day 3 FSH7.6 ± 2.18.0 ± 2.10.21Day 10 FSH8.1 ± 2.18.3 ± 1.10.24Attempt #2.0 ± 1.51.9 ± 1.10.55# Embryos8.0 ± 2.78.3 ± 4.40.31# Transferred3.9 ± 1.53.3 ± 1.30.10Implantation9.0%11.1%0.52Total # Embryos366380% ≥8 cells1242.1%35.5%0.07<8-cell Frag<10%41.1%40.1%0.8310–25%29.0%26.7%0.60>25%30.0%33.2%0.47≥8-cell Frag<10%58.4%63.0%0.4310–25%30.5%25.2%0.31>25%11.0%11.8%0.60 Open table in a new tab Conclusions: The application of IVF for women with infertility and RPL results in similar pregnancy rates to patients with tubal disease utilizing ART. Furthermore, embryos derived from patients with RPL do not exhibit decreased quality as compared with those from tubal factor patients. A history of RPL does not diminish the likelihood of a successful pregnancy following IVF.

Objectives: Many potential etiologies have been proposed for recurrent pregnancy loss (RPL) including elevated levels of androgens and LH. Furthermore, the Polycystic Ovarian Syndrome, defined as ovulatory dysfunction in the setting of clinical or laboratory signs of androgen excess, has been linked to RPL. The objective of this study was to determine whether inherent dysregulation in steroid dynamics, independent of PCOS, exist in women with recurrent pregnancy loss. Design: Prospective observational study. Materials and Methods: Fourteen patients with a history of two or more consecutive, unexplained pregnancy losses before 12 weeks of gestation, with regular ovulatory cycles, luteal phases of at least 10 days, and no clinical evidence of hyperandrogenism were assessed. Genetic, anatomic, infectious, and immunologic etiologies were excluded. Regularly cycling, healthy women (N = 118) with no history of pregnancy loss served as controls. Morning blood samples were obtained throughout the cycle and assayed for LH, FSH, estradiol, and progesterone. Testosterone, DHEAS, 17-OH progesterone, and SHBG were obtained in the early follicular, mid-luteal and ovulatory phases. The data were centered on the day of the LH surge. The LH surge was determined by a combination of the LH, FSH, and estradiol peak, as well as a doubling or exceeding 0.6 ng/ml of the progesterone level. Baseline ultrasounds were performed to identify polycystic ovarian morphology by a single examiner (JMA). (Fig. 1) Results: Patients with a history of RPL demonstrated a decreased SHBG, and an increased Free Testosterone Index. No difference in serum LH, FSH, estradiol, progesterone, 17-OH progesterone or DHEAS were noted throughout the cycle. Nine of the 13 patients had PCO morphology. No differences in the hormonal profile were noted among study subjects with and without PCO. Tabled 1SHBGRPLControlp valueFollicular78.7 ± 11.2130.8 ± 12.50.005Ovulation83.8 ± 13.8129.4 ± 15.40.04Luteal79.3 ± 12.6137.8 ± 13.40.005Free Testosterone IndexRPLControlp valueFollicular1.46 ± 0.380.63 ± 0.080.05Ovulation2.02 ± 0.460.92 ± 0.090.04Luteal1.75 ± 0.360.67 ± 0.080.01 Open table in a new tab Conclusions: Patients with Recurrent Pregnancy Loss display hyperandrogenemia throughout the menstrual cycle independent of PCO morphology. No dysregulation in cycle hormone dynamics or elevation in LH was observed in the RPL study population.