Endogenous progesterone levels could predict reproductive outcome in frozen embryo replacement cycles supplemented with synthetic progestogens: A retrospective cohort study.

PURPOSE: A retrospective, cohort study was conducted between 2009 and 2017 in a private infertility center to determine the predictive value of endogenous estrogen (E2) and progesterone (P4) levels in hormone-replacement frozen embryo replacement (FER) treatment cycles. METHODS: A total of 120 consecutive, infertile patients who became pregnant after FER cycles were analyzed (age: 37.4 ± 4.4 years). Electively vitrified blastocysts were created during natural cycle IVF or mild ovarian stimulation treatments and subsequently transferred through delayed vitrified-thawed blastocyst transfer cycles supplemented with estrogens and a combination of synthetic progestogens. Serum E2 and progesterone P4 levels were intensively monitored every five days (from the day after embryo transfer until 9w1d of pregnancy) and compared among patients with a subsequent live birth (n = 76) or first-trimester pregnancy loss (n = 44). RESULTS: Endogenous placental activity started as early as 5-6th pregnancy week differing significantly according to pregnancy outcome. For P4, the exponential rise from 6w2d onwards allowed distinguishing between failing and successful conceptions. For P4, lower quartiles of the live birth group did not intersect with upper quartiles of the miscarriage group. CONCLUSIONS: Innovative FER protocols incorporating synthetic progestogens allow the correct measurement of endogenous placental activity and could help to monitor early first-trimester ART pregnancies.

Predicting live birth by combining cleavage and blastocyst-stage time-lapse variables using a hierarchical and a data mining-based statistical model.

Prolonged embryo culture is increasingly used as a way of improving pregnancy rates, especially in the context of single embryo transfer. So far, only a handful of studies examined the relation between implantation potential and time-lapse parameters extracted from later stages (morula and blastocyst) of embryo development. For this retrospective study all 285 single vitrified-thawed blastocyst transfers (SVBT) from all consecutive unselected patients whose fertilized oocytes were submitted to time-lapse monitoring (TLM) from a two-year cohort were analysed. Two different statistical models were created; a hierarchical one including the two strongest live birth (LB) predictors (t2 and texpB2) and a more complex model based on principal component analysis (PCA) and logistic regression methods. The first, four-category, hierarchical model effectively distinguished between blastocysts of increasing LB rates (8, 30, 40, 53%). For the second data-mining model quartiles of the created Sc parameter had increasing LB rates (12, 19, 40, 49%). AUC values were comparable for both models (0.723, 95CI%:0.66-0.79 versus 0.717, 95CI%:0.65-0.78). The combination of cleavage- and blastocyst-stage variables through hierarchical or data mining-based algorithms was used successfully to predict live birth. However, due to the lack of internal / external validation the predictive capacities of this model could differ largely in different datasets.

Blastocyst collapse is not an independent predictor of reduced live birth: a time-lapse study.

OBJECTIVE: To ascertain the rate of blastocyst collapse observed by time-lapse monitoring in a retrospective cohort of unselected infertile patients undergoing single blastocyst transfer and to determine its association with live birth. DESIGN: Blastocyst collapse and morphokinetic variables were scored according to previously published criteria. The association between blastocyst collapse and live birth was evaluated by a multivariate logistic regression analysis including morphokinetic variables and other confounders. SETTING: Private infertility clinic. PATIENT(S): Patients who underwent 277 consecutive single blastocyst transfers (mean age, 38.4 ± 3.9 years; range, 28-47 years) after minimal ovarian stimulation. INTERVENTION(S): Minimal ovarian stimulation, prolonged embryo culture in time-lapse monitoring incubator, elective vitrification with subsequent vitrified-warmed single blastocyst transfer. MAIN OUTCOME MEASURE(S): Live birth rate per single blastocyst transfer in different blastocyst collapse groups (no, single, multiple collapses). RESULT(S): No, single, or multiple blastocyst collapses occurred in 54% (150/277), 22% (61/277), and 24% (66/277) of the cohort, respectively. In the multiple collapse group on average 2.9 contractions were seen (range, 2-9 contractions). Live birth rate decreased progressively between blastocyst collapse groups (36%, 31%, 14%); significantly lower if multiple collapses occurred. In a multivariate analysis, however, blastocyst collapse was not found to be a significant predictor and was confounded by stronger predictors such as morphokinetic variables t2, texpB2, and female age. CONCLUSION(S): Blastocyst collapse pattern should not be evaluated alone without taking into account morphokinetic variables that are stronger predictors of reproductive outcome.

Time-lapse variables and embryo gender: a retrospective analysis of 81 live births obtained following minimal stimulation and single embryo transfer.

PURPOSE: The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation. METHODS: Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9 ± 3.8 years, range 28-46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012-2014. Early (PNf, t2-t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB1, and texpB2) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms. RESULTS: Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0-7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB1, and texpB2. The proportion of female embryos was 69-71 and 25-26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74-78 % of them, increasing their proportion by 57 % compared to the average. CONCLUSIONS: Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.