Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial

Background In previous retrospective studies, low serum progesterone level on the embryo transfer day is associated with lower clinical pregnancy and ongoing pregnancy rates. Whether adding progesterone in low serum progesterone patients can rescue the outcome, there is no sufficient evidence from randomized controlled studies. Methods This trial is a clinical randomized controlled study (high serum progesterone vs low serum progesterone 1:1, 1:1 randomization ratio of intervention vs the control group with low serum progesterone). The eligible hormone replacement therapy—frozen embryo transfer (HRT-FET) cycles, will be recruited and randomly assigned to two parallel groups when serum progesterone is < 7.24μg/l on the day of embryo transfer for D3. The intervention group will be extrally given intramuscular progesterone 40 mg per day from D3 to 8 weeks of gestation if clinical pregnancy. The primary outcome is the ongoing pregnancy (beyond 12 weeks of gestation) rate. Discussion The findings of this study will provide strong evidence for whether the progesterone addition from the D3 in low serum progesterone patients can improve the outcome in the HRT-FET cycle. Trial registration ClinicalTrials.govNCT04248309. Registered on January 28, 2020

Role of uterine artery Doppler indices for predicting intrauterine pathology inconclusive on 2-dimensional transvaginal imaging among infertile women undergoing frozen embryo transfer cycle

Background: Objective of current study was to correlate uterine artery Doppler parameters with endometrial findings on hysteroscopy and its importance for the prediction of intrauterine pathology inconclusive on 2-dimensional transvaginal imaging prior to frozen embryo transfer.Methods: This was a retrospective study conducted at Medicover fertility center, New Delhi, India. The study population comprised of women with infertility who have undergone hysteroscopy before frozen embryo transfer. Total 70 patients were recruited based on inclusion/exclusion criteria. Intrauterine pathology found in 57.2% (n= 40) patients and 42.8% (n=30) had normal endometrial cavity on hysteroscopy, they were categorized as group 1 and group 2 respectively based on their findings. Both the groups were compared for pre hysteroscopy uterine artery Doppler parameters, resistivity index and pulsatility index. Further clinical pregnancy rate and miscarriage rate were determined in both groups.Results: Both the groups were comparable for age, body mass index, duration, and type of infertility. Mean RI and PI was significantly higher in group 1 as compared to group 2 (0.90±0.025, 2.89±0.291 vs. 0.76±0.043, 1.82±0.27; p value <0.001). The best cut-off value of uterine artery RI was ≥0.87 with sensitivity of 90% (95% CI=0.7634-0.9721), specificity of 100% (95% CI=0.8843-1.0000) and PI was 2.46 with sensitivity of 100% (95% CI=0.9119-1.0000), specificity of 96.7% (95% CI=0.8278-0.9992).Conclusions: Uterine artery Doppler is a non-invasive, cost- effective useful add-on tool for routine endometrial evaluation and can be a good predictor for screening intrauterine pathology and valuable in decision making for pre-IVF hysteroscopy.

Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment

Background The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. Methods Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA− group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. Results There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. Conclusion The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

A Study on the Prediction of Reproductive Outcomes in Frozen Embryo Transfer Cycles by Calculating the Volume of Uterine Junctional Zone with Three-Dimensional Ultrasound

Purpose To prospectively study the influence of the volume of the uterine junctional zone (JZ) as a novel predictor of reproductive outcomes in frozen embryo transfer cycles. Methods Among the first 30 patients, intra- and interobserver repeatability was evaluated and expressed as a coefficient of repeatability. The same classification system was used to evaluate the JZ of 142 infertility patients undergoing in vitro fertilization (IVF). Ultrasonography was performed on the day before transplantation. The three-dimensional (3D) volume images were then analyzed to obtain the volume of the endometrium (EV), the average thickness of the JZ on the coronal plane, and the volume of the JZ (JZV). The JZV was then divided by the EV. These parameters were compared with the outcomes of clinical pregnancy. Results The 3D image showed that the JZ achieved a good intra- and interobserver consistency (k = 0.862, k = 0.694). The total pregnancy rate was 47%. There was a highly significant difference between pregnant and non-pregnant women with respect to age (p < 0.001), JZV (p = 0.003), and JZV/EV (p < 0.001) on the day before transplantation. Age and JZV/EV were independent factors for predicting the success of IVF transplantation (p = 0.010, p = 0.016). The area under the ROC curve of JZV/EV in predicting clinical pregnancy was 0.688, the cut-off value was 0.54, the sensitivity was 83.8%, and the specificity was 50.0%. Conclusion Age and JZV/EV are independent factors for predicting the success of frozen embryo transfer cycles in IVF. A smaller JZV/EV was more beneficial for clinical pregnancy.