The association between the type of progesterone supplementation and miscarriage risk in women who have had a positive pregnancy test following embryo transfer: a retrospective cohort study.

PURPOSE: The purpose of this study was to identify if switching from intramuscular (IM) to vaginal progesterone compared to staying on IM progesterone after a positive pregnancy test following embryo transfer (ET) is associated with miscarriage risk. METHODS: A retrospective cohort study was performed in a private university-affiliated fertility clinic and included women aged 18-50 years with a positive pregnancy test following ET. The two groups studied were: women who stayed on IM progesterone following a positive pregnancy test and those who switched to vaginal progesterone after a positive test. The main outcome measured was risk of miscarriage < 24 weeks gestation as a proportion of non-biochemical pregnancies. RESULTS: 1988 women were included in the analysis. Among the baseline characteristics, the presence of prior miscarriages as well as prior failed ETs, and frozen cycles (vs fresh) as type of transfer were associated with IM progesterone use (p values ≤ 0.01). As per miscarriage risk < 24 weeks, 22.4% (274/1221) of patients in the IM progesterone group experienced a miscarriage compared with 20.7% (159/767) in the vaginal progesterone group (OR 0.90; 95% CI 0.73-1.13). A multivariable logistic regression model revealed an adjusted OR (aOR) of 0.97 (95% CI 0.77-1.22). CONCLUSION: This study suggests that switching from IM to vaginal progesterone after a positive pregnancy test following an ET is not associated with miscarriage risk. Considering that IM progesterone imposes substantial discomfort, this study offers reassurance and some flexibility in treatment protocols. Further prospective studies are necessary to corroborate the results of this study.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

In freeze-all embryo cycles due to endometrial fluid (EF), live birth rates are comparable to those of controls, despite high rates of EF recurrence and cycle cancellation.

RESEARCH QUESTION: Do cumulative live birth rates (CLBRs) differ between women who have had a freeze-all embryo cycle (FAE) for endometrial fluid (EF) and controls? DESIGN: This retrospective cohort study included 83 women who had a FAE cycle due to the presence of EF between 2010 and 2016 at a university-affiliated private IVF center. The controls were 219 women who had FAE for other indications during the same period and were randomly selected. The main outcome measures were CLBRs, EF recurrence, cancellation and pregnancy loss rates. RESULTS: Population characteristics were comparable between the two groups. The CLBR was not significantly different between the EF and the control group: 39.8 % vs. 47.0 %, respectively, p=0.26. Cancellation rates in the two first FETs were higher in the EF group than the control group: 18.1 % vs. 4.1 % (p<0.001) and 22.9 % vs. 8.5 % (p=0.02). After FAE for EF, we observed a significant risk of EF recurrence (32/177 cycles, 18.1 %), allowing us to identify a poor prognosis subgroup. When EF was detected, the LBR per transfer was 7.1 % (1/14) when the transfer was finally performed (after EF aspiration or EF disappearance), compared to 25 % (32/128) in cycles without EF recurrence (p<0.05). Conversely, in the absence of EF recurrence (145/177, 81.9 %), the LBR was comparable to that of the control group. The type of endometrial preparation does not seem to be associated with EF recurrence. CONCLUSION: Despite higher rates of EF recurrence and cycle cancellation, women with FAE for EF ultimately have comparable LBRs to those who have had a FAE for other indications. However, women presenting with at least one EF recurrence during FETs seem to have a lower LBR.

Effect of uterine dimensions on live birth rates after single embryo transfer in infertile women.

RESEARCH QUESTION: Do uterine size parameters measured by baseline transvaginal ultrasound predict live birth after single embryo transfer (SET) of a high-quality blastocyst? DESIGN: Retrospective cohort study including women undergoing their first SET between August 2010 and March 2014 at a large university hospital reproductive centre. The effects of baseline uterine dimensions on live birth rate (LBR) were analysed while controlling for confounding effects. RESULTS: A total of 437 nulliparous and 70 parous women were included. The nulliparous group had lower body mass index (BMI) (24.4 ± 5.1 versus 25.9 ± 4.5 kg/m2; P = 0.015) and a higher number of fibroids (0.4 ± 1.0 versus 0.2 ± 0.5; P = 0.005) than the parous group. While controlling for confounding effects, none of the uterine parameters appeared to be a significant predictor of LBR among nulliparous and parous women (P > 0.05 in all cases). A subsequent analysis of endometrial length was done, whereby the endometrial lengths were divided into quartiles (20.0-32.2 mm; 32.3-36.5 mm; 36.6-40.0 mm; 40.1-54.0 mm). After controlling for confounders, the shortest quartile in the nulliparous group had a significantly lower LBR (P = 0.02) than the other groups. Receiver operating characteristic curves suggested that endometrial cavity length and cervical length did not aid clinically. CONCLUSION: Uterine parameters do not have a clinically useful impact on LBR after SET of a blastocyst in infertile women. The use of baseline endometrial length to predict live birth is no better than chance, while cervical length only predicts failure to live birth.

A comparison of IVF outcomes transferring a single ideal blastocyst in women with polycystic ovary syndrome and normal ovulatory controls.

PURPOSE: To assess the effects PCOS on live birth rates when transferring a single fresh ideal blastocyst. METHODS: A retrospective cohort study performed at the university-affiliated reproductive center. Women with PCOS and a control group of normal ovulatory women who underwent their first fresh embryo transfer with single ideal grade blastocyst were included in the study. Demographic, stimulation information and pregnancy outcomes were collected and analysed. The primary outcome was live birth rates, and secondary outcomes included pregnancy and clinical pregnancy rates. RESULTS: 71 Women with PCOS and 272 normal ovulatory controls underwent their first embryo transfer and met the inclusion and exclusion criteria. PCOS patient were younger (31.0 ± 3.7 vs. 33.1 ± 3.2, p = 0.0001), with higher AFC (40.0 ± 9.3 vs. 13.3 ± 4.6, p = 0.0001), required lower dose of gonadotropins to stimulate (1198 ± 786 vs. 1891 ± 1224, p = 0.0001), and had higher serum testosterone levels (2.3 ± 0.7 vs. 1.1 ± 0.3, p = 0.0001). No significant difference was found between the two groups regarding the number of previous pregnancies, the number of previous full-term pregnancies, the level of basal serum FSH, estradiol level at triggering and the BMI. When compared by Chi squared testing pregnancy rates, clinical pregnancy rates and live birth rates did not differ. However, when controlling (with multivariate stepwise logistic regression) for confounders, live birth rates were lower among the women with PCOS (p = 0.035, CI: 0.18-0.92). CONCLUSION: After controlling for confounders, when transferring a fresh single ideal blastocyst, live birth rates were lower among the women with PCOS than normal ovulatory controls.

Outcomes of Preimplantation Genetic Testing for Single Gene Defects in a Privately Funded Period and Publicly Funded Period: A North-American Single Center Experience.

BACKGROUND: The purpose of this study was to assess whether the outcomes from IVF-preimplantation genetic testing (IVF-PGT) cycles for single gene defects (SGD) (PGT-M) differ between a privately funded period (PRP) and publicly funded period (PUP). METHODS: A retrospective cohort study was conducted in a North-American single tertiary center. The PRP (March 1998 to July 2010) comprised 56 PGT-M cycles from 58 IVF cycles in 38 couples, and the PUP (August 2010 to May 2015) comprised 59 PGT-M cycles from 87 IVF cycles in 38 couples. One PGT-M cycle is defined as one biopsy procedure from one or serial IVF cycles. A p-value of 0.05 was considered statistically significant. RESULTS: The clinical pregnancy rates (CPR) per PGT-M cycle were 30.4% and 52.5% in each period, respectively (p=0.021). The live birth rates (LBR) per PGT-M cycle were 21.5% versus 40.9% in each period, respectively (p=0.037). A sub-analysis within the PUP comparing 39 PGT-M cycles from 39 IVF cycles with 20 PGT-M cycles from 49 IVF cycles yielded CPRs per PGT-M cycle of 64.1% and 30.0% and LBRs per PGT-M cycle of 53.8% and 15.0%, in each group, respectively (p< 0.05 for both). CONCLUSION: The transition from private to public funding and a single embryo transfer (ET) guideline has little impact on embryological and clinical outcomes of PGT-M cycles, and results in lower rates of multiple pregnancies. However, these two systems may serve different populations.

Does ovarian reserve affect outcomes in single ideal blastocyst transfers in women less than 40 years of age?

PURPOSE: There is much debate whether diminished ovarian reserve is purely a quantitative issue, or if quality as determined by pregnancy potential of the ensuing oocytes is also affected. The purpose of this study was to determine whether diminished ovarian reserve, as established by one of three ways described below, affects pregnancy outcomes of women under 40 years old undergoing a single ideal blastocyst transfer. MATERIALS AND METHODS: This was a retrospective cohort study, including 507 women undergoing an ideal quality single embryo transfer between August 2010 and March 2014. Logistic regression was used to control for age, duration of infertility, parity, body mass index, and smoking status. For analysis, women were stratified for: antral follicle counts (≤ 5 vs. > 5), basal serum FSH levels (< 13 vs. ≥ 13 IU/L), and quartile of total FSH dose required for stimulation. RESULTS: In stratifying women by antral follicle count (AFC) ≤ 5 vs. > 5, the pregnancy rate (40 vs. 53%, p = 0.04), clinical pregnancy rate (29 vs. 46%, p = 0.02), and live birth rate (13 vs. 43%, p = 0.001) were superior with AFC > 5. Using FSH levels (< 13 vs. ≥ 13 IU/L), the pregnancy rate (50 vs. 31%, p = 0.27), clinical pregnancy rate (40 vs. 13%, p = 0.45), and live birth rate (38 vs. 13%, p = 0.48) were similar. Examining quartiles of FSH stimulation, the pregnancy rates were similar (from lowest to highest: 45, 52, 54, 41%, p = 0.13); however, clinical pregnancy rate (36, 43, 47, 25%, p = 0.003) and live birth rate (32, 38, 44, 20%, p = 0.005) were superior in lower quartiles vs. the highest quartile. CONCLUSION: Ovarian reserve may affect embryo pregnancy potential and outcomes when measured by AFC and exogenous stimulation but not by basal FSH levels.