Clinical Pregnancy Loss Rate Research Articles

Effect of postthaw change in embryo score on single euploid embryo transfer success rates

ObjectiveTo assess whether the change in embryo morphology from pre-cryopreservation to post-thaw is associated with embryo transfer success rates in single euploid embryo transfer cycles. DesignRetrospective cohort study SubjectsPatients who underwent a single euploid embryo transfer cycle from September 2016 – April 2022 were included. A decision support tool was used to assign each embryo a reproductive potential score based on the day of biopsy, expansion, and grade of trophectoderm and inner cell mass (ICM) at the time of cryopreservation and post-thaw.(1) Embryos were divided into 4 groups: Group 1 included embryos with the same score post-thaw (reference), Group 2 higher score, Group 3 lower score, and Group 4 embryos that did not re-expand post-thaw. Intervention(s)No interventions administered. Main Outcome MeasuresPrimary outcome was live birth rates per embryo transfer (LBR). Secondary outcomes included chemical pregnancy, clinical pregnancy, and clinical pregnancy loss rate. Comparative statistics and univariate analyses were performed using Kruskal-Wallis and chi-square tests. Multivariate logistic regression fitted with generalized estimating equation was performed to compare the odds of live birth between groups. ResultsA total of 7750 embryo transfers performed for 4613 patients met inclusion criteria: 5331 in Group 1, 486 in Group 2, 1726 in Group 3, and 207 in group 4. On univariate analysis, there was a statistically significant difference in LBR between groups 1, 2, 3, and 4 (55.8% vs 51.4%, 47.5%, 26.6%, p<0.0001). Logistic regression controlling for oocyte age, AMH, BMI, endometrial thickness, year of embryo transfer, time from thaw to final grading, and embryo score prior to cryopreservation showed significantly lower odds of LBR when the embryo was downgraded (OR 0.70, CI 0.62-0.79, p=<.0001) or did not re-expand (OR 0.36, CI 0.26-0.51 p=<.0001) compared with no change in score. When controlling for all variables, there was a significant increase in odds of live birth between embryos that had higher score post-thaw versus those without a change (OR 1.42, CI 1.14-1.76, p=0.002). There was no significant difference in clinical pregnancy loss rate among the 4 groups. ConclusionsThe change in quality of the embryo post-thaw is an important factor in embryo transfer success. In an adjusted analysis, the chemical pregnancy, clinical pregnancy, and LBR per embryo transfer are all significantly decreased in embryos that were downgraded or did not expand on the day of single euploid embryo transfer. Embryos that re-expand and improve their quality post-thaw have the highest odds of live birth.

Comparative analysis of pregnancy outcomes in preimplantation genetic testing for aneuploidy and conventional in vitro fertilization and embryo transfer: a stratified examination on the basis of the quantity of oocytes and blastocysts from a multicenter randomized controlled trial

To investigate variations in pregnancy outcomes between preimplantation genetic testing for aneuploidy (PGT-A) and conventional invitro fertilization and embryo transfer (IVF-ET) treatment across distinct groups categorized by oocyte and blastocyst counts. Because the live birth rate (LBR) of assisted reproductive technology treatment is influenced by the number of oocytes and blastocysts retrieved. Our previous study indicated comparable cumulative LBRs (CLBRs) between conventional IVF-ET and PGT-A. A post hoc exploratory secondary analysis of data from a multicenter randomized controlled trial compared the CLBRs between conventional IVF-ET and PGT-A. Academic fertility centers. A total of 1,212 infertile women with a good prognosis for a live birth after PGT-A or conventional IVF-ET were included. Women underwent PGT-A or conventional IVF-ET. Cumulative LBR, cumulative clinical pregnancy loss (CPL) rate, and good birth outcome. In the study, all participants were divided into 4 groups on the basis of quartiles of the number of oocytes retrieved, or blastocysts. There was an interaction between whether to perform PGT-A and the oocyte numbers category on cumulative CPL and biochemical pregnancy loss. Chi-square analysis revealed that the PGT-A group showed a lower cumulative frequency of CPL compared with the IVF-ET group (PGT-A vs. IVF-ET: 5.9% vs. 13.7%; relative risk = 0.430; 95% confidence interval, 0.243-0.763) when the number of oocytes retrieved was <15. Although there was no interaction on CLBR when the retrieved oocyte count ranged from 19-23 (19≤ oocytes <23) the PGT-A group exhibited a lower CLBR than the conventional IVF-ET group (PGT-A vs IVF-ET: 75.6% vs 87.1%; relative risk = 0.868; 95% confidence interval, 0.774-0.973), and the average body weight of newborns from the PGT-A group was approximately 142 g lower than that of the conventional IVF-ET group (PGT-A vs. IVF-ET: 3,334 ± 479 g vs. 3,476 ± 473 g). However, no statistically significant difference in the CLBR was observed between the PGT-A and IVF-ET groups in the other oocyte or blastocyst groups. When the number of retrieved eggs was <15, the PGT-A group exhibited a lower cumulative CPL rate but no higher CLBR than the conventional IVF-ET group. NCT03118141.

Single Euploid Embryo Transfer Outcomes After Uterine Septum Resection

ObjectiveTo study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without Müllerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries. DesignRetrospective cohort study SettingSingle academic affiliated center Patients60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET between 2012-2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group. Intervention(s)No interventions administered. Measurements and Main ResultsPregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with history of uterine septum resection compared to matched patients without Müllerian anomalies or uterine surgeries. Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p=0.004), implantation (41.67% vs 65.6%, p=0.001), and live birth (33.33% vs 57.8%, p=0.001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p=0.89). ConclusionPatients with history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared to patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without, however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET and to optimize their reproductive outcomes.

The impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes in patients with unexplained recurrent pregnancy loss

Objective: To investigate the impact of the number of previous miscarriages on embryo euploid rate and pregnancy outcomes after preimplantation genetic testing for aneuploidies (PGT-A) in patients with unexplained recurrent pregnancy loss (uRPL). Methods: A retrospective cohort study was conducted. 799 women with uRPL who underwent PGT-A for the first time between January 2015 and December 2021 at the Reproductive center of Shandong University were enrolled. These patients were divided into three groups according to the number of previous miscarriages (2, 3, and≥4). Stratified analysis was conducted according to female age (≤37 years and>37 years). The embryo euploidy rate, good-quality blastocyst formation rate, cumulative live birth rate, and cumulative clinical pregnancy loss rate of three groups were compared in younger and older patients, respectively. Meanwhile, the cumulative live birth rate, clinical pregnancy loss rate, and embryo euploidy rate were analyzed by multivariate logistic regression analysis. Results: Patients' age was (34.7±5.1) years old. In the three groups with 2, 3 and ≥4 previous miscarriages, there was no significant difference in the embryo euploidy rate between groups in the younger [48.9% (539/1 103), 50.6% (354/700) and 52.1% (152/292), P=0.567] and older [26.2% (103/393), 28.8% (55/191) and 20.5% (16/78), P=0.377] age population. Compared with 2 and 3 previous miscarriages, the cumulative live birth rate was significantly decreased [52.6% (153/291), 52.8% (93/176) and 34.3% (25/73), P=0.014] and the cumulative clinical pregnancy loss rate was significantly increased [15.8% (31/196), 15.3% (18/118) and 46.9% (23/49), P<0.001] in younger women with ≥4 miscarriages. After adjusting for maternal age, BMI, AMH, endometrial thickness on hCG trigger day and antral follicle count, the number of previous miscarriages ≥4 was a relevant factor for cumulative live birth rate (OR=0.461, 95%CI: 0.263-0.807, P=0.007) and the cumulative clinical pregnancy loss rate (OR=4.382, 95%CI: 2.165-8.873, P<0.001) in younger patients, but it was not significantly correlated with the cumulative live birth rate, cumulative clinical pregnancy loss rate and embryo euploidy rate in patients with advanced age. Conclusion: In uRPL patients,≥4 previous miscarriages decreased cumulative live birth rate and increased cumulative clinical pregnancy loss rate in women aged≤37 years old.

Recent clomiphene citrate exposure does not impact subsequent clinical outcomes in single euploid frozen embryo transfer cycles

Do infertile couples who recently utilized clomiphene citrate (CC) for ovulation induction or ovarian stimulation (<90 days previously) followed by a single euploid embryo transfer (SEET) have lower implantation potential compared with patients who were not exposed to CC within 90 days before embryo transfer (ET)? There does not appear to be an association between recent CC exposure and lower implantation potential in patients who undergo a frozen embryo transfer (FET) of euploid embryos. Clomiphene has been found to be associated with lower pregnancy rates when compared against other ovarian stimulation medications. The majority of published research about the effects of CC on implantation potential suggest an anti-estrogenic effect on the endometrium. Quality evidence and information about utilization of CC and its effect on implantation potential after euploid ETs is lacking in the literature. A retrospective cohort study with propensity score matching was carried out. We included all patients that underwent an autologous SEET from September 2016 to September 2022 at a single academic-private ART center. The study group included patients that had utilized CC during either ovulation induction cycles and/or controlled ovarian stimulation at least 90 days before FET. A propensity score-matched control group of patients that were unexposed to CC within 90 days prior to SEET was used for comparisons. The primary outcome was positive pregnancy test (defined as a positive serum β-hCG measured 9 days after ET), with other outcomes including clinical pregnancy, ongoing pregnancy, biochemical pregnancy loss, and clinical pregnancy loss rates per SEET. Multivariate regression analyses fitted with generalized estimating equations were utilized to analyze if there was an association between CC utilization and IVF outcomes. Furthermore, the study evaluated the cumulative effect of CC and endometrial receptivity in vivo and subsequent IVF outcomes. A total of 593 patients with utilization of CC in <90 days before ET were compared with 1779 matched controls. Positive pregnancy test rates were comparable among the control group and the CC exposed groups, respectively (74.3% versus 75.7%, P = 0.79), as were clinical pregnancy (64.0% versus 65.0%, P = 0.60), ongoing pregnancy (51.8% versus 53.2%, P = 0.74), biochemical pregnancy loss (15.7% versus 14.03%, P = 0.45), and clinical pregnancy loss rates were also comparable among cohorts (17.1% versus 18.1%, P = 0.71). No association was found between utilization of clomiphene and lower implantation rates (adjusted odds ratio 0.95, 95% CI 0.76-1.18). Also, no differences were observed in sub-analyses based on multiple CC utilization periods. Finally, no association was found between the number of consecutive cumulative clomiphene cycles and sub-optimal IVF outcomes. The study has inherent bias that originated from its retrospective design. Serum levels of CC were not measured and sample size for the sub-analyses was small. There does not appear to be an association between recent CC exposure and lower implantation potential in patients who undergo a FET of euploid embryos. This finding remains consistent, even in patients who undergo multiple, consecutive clomiphene cycles prior to ET. There were no long-term effects of CC on endometrial development and clinical characteristics examined in this study. Patients that utilized CC medication prior to a SEET cycle for either ovarian stimulation or ovulation induction, can be assured that there is no evidence of a residual effect of recent CC administration that could jeopardize their pregnancy probability. No funding was received for the realization of this study. A.C. is advisor and/or board member of Sema4 (stakeholder in data) and Progyny. The other authors have no conflicts of interest to declare. N/A.

Transfer of the fittest: using preimplantation genetic testing for aneuploidy to select embryo(s) most likely to lead to live birth

Preimplantation genetic testing for aneuploidy (PGT-A) was developed to identify euploid embryos from a cohort of embryos with unknown ploidy produced during an invitro fertilization (IVF) cycle. In recent years, the ability of PGT-A to improve IVF outcomes has come into question. The goal of this review was to summarize the major randomized controlled trials (RCTs) and nonselection studies evaluating the benefit of PGT-A to improve the live birth rates (LBRs). We argue that the LBR per transfer is more relevant to the individual patient than the cumulative LBR as a means to minimize the burden of IVF by reducing futile transfers, pregnancy losses, and ongoing aneuploidy. The early RCTs demonstrate improved implantation rates and LBRs with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by the small sample size and a bias toward good-prognosis patients. Further studies using next-generation sequencing found more variable results but did confirm an improvement in the LBRs per transfer in an older population with a higher baseline risk of aneuploidy. The largest RCT to date showed similar cumulative LBRs in the PGT-A and control groups after biopsy and sequential transfer of up to 3 blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Nonselection studies evaluating pregnancy outcomes after transfer of euploid vs. aneuploid embryos demonstrate near-perfect negative predictive value for an aneuploid result to predict live birth. Putative mosaic embryos had similar LBRs compared with euploid embryos. The available RCTs and nonselection studies support the practice of using PGT-A to identify euploid embryos for transfer, especially in an older population, while simultaneously selecting against aneuploid embryos, without negative impact on the total reproductive potential of the cycle.

P-312 Effect on pregnancy outcomes of depot GnRH agonist pre-treatment before frozen-thawed embryo transfer cycles in patients with adenomyosis

Abstract Study question Is there any difference between using or not using depot GnRH agonist pre-treatment on pregnancy outcomes in patients with adenomyosis before frozen-thawed embryo transfer cycles? Summary answer GnRH agonist pre-treatment before frozen-thawed embryo transfer has no effect on pregnancy outcomes in adenomyosis patients. What is known already Uterine adenomyosis negatively affects implantation and clinical pregnancy rates and also increases the risk of early pregnancy loss. Increased inflammatory markers and increased myometrial peristalsis are thought to decrease the rate of implantation. Depot GnRH agonist pre-treatment is thought to increase implantation rate by both decreasing myometrial contractility and reducing inflammatory marker production. Study design, size, duration This retrospective cohort study was conducted at ART and Reproductive Genetics Centre, Memorial Sisli Hospital, Istanbul, Turkey. Patients with adenomyosis undergoing a FET cycle between 2011 and 2021 were evaluated. Patients between 25-45 years old with good and top-quality blastocysts were included and preimplantation genetic diagnosis (PGD) was applied to patients who were &amp;gt;37 years old. A total of 144 frozen embryo transfer cycles were examined. Participants/materials, setting, methods Diagnosis of adenomyosis was made using transvaginal ultrasound and/or pelvic magnetic resonance imaging which revealed an asymmetrically thickening between the anterior and posterior uterine walls, focal adenomyosis, myometrial cysts and irregular/interrupted junctional zone of the endometrium. 65 patients in the study group (Group I) who received depot GnRH agonist pre-treatment for minimum 2 and maximum 6 months and 79 patients without GnRH agonist pre-treatment (Group 2) were evaluated. Main results and the role of chance There was no significant difference in patient characteristics such as age, endometrial thickness on embryo transfer day, BMI, infertility duration, and anti mullerian hormone levels between groups 1 and 2. Endometrial preparation was done using artificial cycle in the depot agonist group, whereas both artificial and modified natural cycle were used in patients without depot GnRH agonist pre-treatment.The pregnancy rate was 53.8%(n = 35) in group 1 and 54.4%(n = 43) in group 2. The clinical pregnancy loss rate was 20% (n = 9) in group 1 and 15.7% (n = 6)in group 2. The live birth rate was 40% (n = 26) in group I and 39.2. (n = 31) in group II. There were no statistically significant differences in pregnancy rates, clinical pregnancy losses, and live birth rates between the groups. Limitations, reasons for caution The limitation of the study is its retrospective nature. Wider implications of the findings The lack of any statistically significant differences in pregnancy outcomes in this study suggests the need for further evaluation of the value/effectiveness of GnRHa treatment in adenomyosis patients before embryo transfer cycles. Trial registration number not applicable

Biological relevance of trophectoderm morphology: initial β-hCG measurements correlate with trophectoderm grading on euploid frozen embryo transfers.

To analyze the correlation between TE grading and initial β-hCG serum level after single euploid embryo transfer. Secondarily, to explore the association between TE grading with subsequent IVF outcomes. Retrospective cohort analysis. Single, academic, private infertility and assisted reproductive care institute. Infertility patients who underwent a single euploid embryo transfer that resulted in a positive pregnancy test. β-hCG measurements. Correlation between TE grade with first β-hCG measurement. Second outcome measurements included ongoing pregnancy, biochemical pregnancy loss, and clinical pregnancy loss rates. 2,798 cases were analyzed. A significant difference in initial β-hCG measurement among groups (TE A: median 143.4 mIU/mL IQR 79.2-211.2; TE B: 119 mIU/mL IQR 57.1-177.8; TE C: 82.4 mIU/mL IQR 36.3-136.4, p ≤ 0.0001) was observed. There was a significant correlation found between the TE grade and β-hCG measurements (p ≤ 0.0001, r2 = 0.10). TE grade was not associated with higher odds of biochemical pregnancy loss (TE A vs. TE B: aOR 1.01 CI95% 0.97-1.05; TE A vs. TE C: aOR 1.03 CI95% 0.98-1.08), or higher odds of clinical pregnancy loss (TE A vs. TE B: aOR 1.02 CI95% 0.98-1.05; TE A vs. TE C: aOR 1.03 CI95% 0.98-1.07). In patients with euploid embryos, TE grade correlates with the first pregnancy test measurement of β-hCG. We propose this finding helps to appoint a relevant link between morphology assessment and early embryo development in vivo.

Elevated Body Mass Index in Donor Oocyte Recipients Does Not Affect Implantation of Euploid Embryos.

Background: Obesity is a worldwide epidemic that has been shown to have serious implications on health outcomes. Regarding reproductive health, increased body mass index (BMI) reduces fertility and increases the time to conceive. It is unclear how excess weight in females affects the development of oocytes and embryos or the impact of implantation. Materials and Methods: This retrospective single-center study aimed to determine if overweight and obese oocyte recipients had similar pregnancy outcomes compared with healthy weight controls after the transfer of a single euploid frozen-thawed embryo transfer (FET). Five hundred twenty-eight patients who underwent a transfer from 2016 to 2021 were included. The primary outcome studied was the clinical pregnancy (CP) rate. Secondary outcomes included live birth (LB) rate, biochemical pregnancy loss (BPL) rate, and clinical pregnancy loss (CPL) rate. Results: The overall CP rate was 54.9% and did not differ significantly among normal weight (n = 318), overweight (n = 129), and obese (n = 81) BMI categories (0.56 vs. 0.56 vs. 0.49, p = 0.56). There were no significant differences in LB rate (0.47 vs. 0.43 vs. 0.38, p = 0.33), BPL rate (0.14 vs. 0.09 vs. 0.11, p = 0.59), and CPL rate (0.15 vs. 0.21 vs. 0.18, p = 0.38) among BMI groups. Conclusions: Our findings provide support that BMI alone does not adversely alter endometrial receptivity and is not the cause of poor in vitro fertilization (IVF) outcomes in patients with increased BMI. These deleterious IVF outcomes might be to the result of diminished oocyte and/or embryo quality or other factors that have not yet been elucidated.

The Impact of the Coronavirus Disease 19 Pandemic on Early Pregnancy Outcomes Among Patients Undergoing In Vitro Fertilization Treatment.

Objective: To determine if pregnancy rates (PRs) or pregnancy loss rates (PLRs) were altered in patients undergoing single, euploid frozen-thawed embryo transfer (FET) during the initial peak of the Coronavirus Disease 19 (COVID-19) pandemic.Materials and Methods: This was a retrospective cohort study performed in a single academic center. Patients undergoing single, euploid FET cycles from January to May 2017–2020 were included. Cycles with FET performed in January–May of 2020 (“COVID-surge cohort”) were compared to cycles with FET performed in January–May of 2017–2019 (“pre-COVID cohort”). Pregnancy rate (PR), clinical pregnancy rate (CPR), pregnancy loss rate (PLR), and clinical pregnancy loss rate (CLR) were compared between the cohorts.Results: A total of 2629 single, euploid FET cycles were included: 2070 from January to May, 2017–2019 and 559 from January to May 2020. PR was similar when comparing FET performed from January to May 2020 (COVID-surge) to those performed from January to May, 2017–2019 (pre-COVID) (77.6% vs. 73.7%, p = 0.06), while CPR was higher among the COVID-surge compared to the pre-COVID cohort (65.5% vs. 60.0%, p = 0.02). No differences were seen in PLR and CLR among the COVID-surge and pre-COVID cohorts (28.3% vs. 32.0%, p = 0.08; 15.0% vs. 16.5%, p = 0.50). PR, CPR, PLR, and CLR were similar when comparing individual months between the cohorts. Adjusted analysis showed no differences in PR, CPR, PLR, or CLR when comparing the cohorts overall or when comparing corresponding individual months in the two time periods.Conclusion: PRs and PLRs were not decreased when SARS-CoV-2 transmission was widespread in our geographic area, suggesting that high COVID-19 transmission does not compromise early pregnancy outcomes.

THE HYPOTHESIS OF PREFERENCIAL LOSS OF FEMALE EMBRYOS: EMBRYONIC SEX IS NOT ASSOCIATED WITH INCREASED ODDS OF EARLY PREGNANCY LOSS

The human sex ratio has long interested developmental biologists, statisticians, and other scientists. Primary Sex Ratio (PSR) in humans has been thought to be male-biased. Previously published studies about PSR have suggested this bias is due to a preferential loss of female conceptuses during the earliest stages of pregnancy1,2. To date, the dynamics of PSR from conception to birth are poorly understood. Literature about PSR is currently based on subjective estimates, extrapolations from large historical cohorts, or based on data sourced from natural conceptions3. Yet, the use of data from patients who undergo ART treatment presents an opportunity to observe embryonic sex prior to transfer through the application of PGT. This study aims to analyze whether the selection of female embryos prior to frozen embryo transfer (FET) are at higher risk of suffering early pregnancy loss as compared to the selection of male embryos. The study included patients who underwent a single euploid FET cycle from 2016-2021. Gender selection for family balancing cases were excluded from the analysis. PGT-A with NGS was performed for all cases. Cohorts were segregated into groups based on embryonic sex prior to transfer selection. Only top morphology embryos with a grade ≥4AA (Modified Gardner’s) were included in the study. Patient demographics and IVF cycle outcomes were recorded. Biochemical pregnancy loss (BPL) was defined as detectible serum ß-hCG and embryonic arrest prior to the development of a clinical pregnancy. Clinical pregnancy loss (CPL) was defined as the loss of a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs. Comparative statistics and an adjusted mixed model with a GEE were utilized for statistical analyses. A sample size of 906 single, euploid FETs per cohort was calculated to ensure an 80% power to detect a difference of 5% on clinical pregnancy loss rates (α=0.05). 1,363 male were compared to 1,045 female FETs. No differences were found in patient’s age, BMI, AMH, endometrial thickness and other demographic variables between cohorts. Also, no differences were found in implantation, clinical pregnancy, ongoing pregnancy, BPL and CPL. After adjusting for age, BMI, AMH, day of biopsy and endometrial thickness, no association was found between embryo sex and increased odds of BPL (OR 0.50 CI95% 0.11-2.27, p=0.37); or CPL (OR 0.28 CI95% 0.07-1.16, p=0.08). By analyzing a large cohort of single euploid embryo transfers, we can observe the proportion of pregnancy losses that are not associated with aneuploidy, thus assessing the differences on early pregnancy loss rates based on embryonic sex while adjusting for other important covariates. For patients who undergo IVF with subsequent PGT-A and FET, there does not appear to be increased odds of pregnancy loss in selecting a single, euploid female embryo compared to male embryo counterparts.

The impact of indomethacin on the number of oocytes retrieved and IVF outcomes in patients with poor ovarian response

ObjectiveThe aim of this retrospective case-control study was to analyze the effect of administering indomethacin after triggering final oocyte maturation in patients with poor ovarian response (POR) on the cycle cancellation rate due to premature ovulation (PO), the number of oocytes retrieved and the clinical outcomes of IVF cycles. Study DesignA total of 214 patients with POR, diagnosed according to the Bologna criteria, who underwent fresh IVF cycle via flexible gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol were enrolled in the study. The control group consisted of 100 patients, whereas the indomethacin group included 114 patients who received 100 mg rectal indomethacin administered twice within the same day (twelve hours apart) –starting at twelve hours after triggering. Cycle cancelation rates (CCR), number of oocytes retrieved (nOR), implantation rates (IR), biochemical pregnancy (BP) and clinical pregnancy loss rates (CPL), ongoing pregnancy rates (OPR) and live birth rates (LBR) were compared between the indomethacin and control groups. ResultsThe CCR rate was significantly lower in the indomethacin group (1.8%) compared to the control group (1.8% vs %12%, p = 0.01). In the control group, those with cycle cancellation were older than those without cycle cancellation (mean age 42.2 ± 2.3 years vs. 39.36 ± 4.3 years, p = 0.001) and had lower anti-Müllerian hormone levels and lower antral follicle count (0.59 ± 0.2 ng/mL vs 0.79 ± 0.2 ng/mL, p = 0.001 and 4 ± 0.6 vs 5.7 ± 1.7, p = 0.001, respectively). In multivariable analysis, when the dependent variable in the logistic regression model was coded as the absence of cycle cancellation, it was observed that only indomethacin had a statistically significant effect on cycle cancellation (β = −1.931, standard error = 0.832, Exp(B) = 0.145, p = 0.020). nOR was higher in the indomethacin group than control group but the difference did not reach significance (p = 0.07). Moreover, the IR, OPR and LBR, BP and CPL values were similar in the indomethacin and control groups (p > 0.05). ConclusionsBased on data from this study, it can be concluded that indomethacin reduces cycle cancelation due to PO in patients with POR –without compromising implantation and pregnancy rates. However, further randomized controlled trials with larger sample sizes are required to clarify the definitive effect of indomethacin in the treatment of patients with POR.

Late follicular phase progesterone elevation during ovarian stimulation is not associated with decreased implantation of chromosomally screened embryos in thaw cycles

What is the impact of a late follicular phase progesterone elevation (LFPE) during controlled ovarian hyperstimulation (COH) on embryonic competence and reproductive potential in thaw cycles of preimplantation genetic testing for aneuploidy (PGT-A) screened embryos? Our study findings suggest that LFPE, utilizing a progesterone cutoff value of 2.0 ng/ml, is neither associated with impaired embryonic development, increased rate of embryonic aneuploidy, nor compromised implantation and pregnancy outcomes following a euploid frozen embryo transfer (FET) cycle. Premature progesterone elevation during COH has been associated with lower pregnancy rates due to altered endometrial receptivity in fresh IVF cycles. Also, increased levels of progesterone (P) have been suggested to be a marker for ovarian dysfunction, with some evidence to show an association between LFPE and suboptimal embryonic development. However, the effect of LFPE on embryonic competence is still controversial. Retrospective cohort analysis in a single, academic ART center from September 2016 to March 2020. In total, 5244 COH cycles for IVF/PGT-A were analyzed, of those 5141 were included in the analysis. A total of 23991 blastocysts underwent trophectoderm biopsy and PGT analysis. Additionally, the clinical IVF outcomes of 5806 single euploid FET cycles were evaluated. Cohorts were separated in two groups: Group 1: oocytes retrieved from cycles with normal P levels during ovulation trigger (P ≤ 2.0 ng/ml); Group 2: oocytes retrieved after cycles in which LFPE was noted (P > 2.0 ng/ml). Extended culture and PGT-A was performed. Secondly, IVF outcomes after a single euploid FET were evaluated for each cohort. Four thousand nine hundred and twenty-five cycles in Group 1 were compared with 216 cycles on Group 2. Oocyte maturity rates, fertilization rates and blastulation rates were comparable among groups. A 65.3% (n = 22654) rate of utilizable blastocysts was found in patients with normal P levels and were comparable to the 62.4% (n = 1337) observed in those with LFPE (P = 0.19). The euploidy rates were 52.8% (n = 11964) and 53.4% (n = 714), respectively, albeit this difference was not statistically significant (P = 0.81). Our multivariate analysis was fitted with a generalized estimating equation (GEE) and no association was found with LFPE and an increased odds of embryo aneuploidy (adjusted odds ratio 1.04 95% CI 0.86-1.27, P = 0.62). A sub-analysis of subsequent 5806 euploid FET cycles (normal P: n = 5617 cycles and elevated P: n = 189 cycles) showed no differences among groups in patient's BMI, Anti-Müllerian hormone (AMH), endometrial thickness at FET and number of prior IVF cycles. However, a significant difference was found in patient's age and oocyte age. The number of good quality embryos transferred, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate and clinical pregnancy loss rates were comparable among groups. Of the registered live births (normal P group: n = 2198; elevated P group: n = 52), there were no significant differences in gestational age weeks (39.0 ± 1.89 versus 39.24 ± 1.53, P = 0.25) and birth weight (3317 ± 571.9 versus 3 266 ± 455.8 g, P = 0.26) at delivery, respectively. The retrospective nature of the study and probable variability in the study center's laboratory protocol(s), selected progesterone cutoff value and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. Based on robust sequencing data from a large cohort of embryos, we conclude that premature P elevation during IVF stimulation does not predict embryonic competence. Our study results show that LFPE is neither associated with impaired embryonic development nor increased rates of aneuploidy. Embryos obtained from cycles with LFPE can be selected for transfer, and patients can be reassured that the odds of achieving a healthy pregnancy are similar to the embryos exposed during COH cycles to physiologically normal P levels. No funding was received for the realization of this study. Dr A.B.C. is advisor and/or board member of Sema 4 (Stakeholder in data), Progyny and Celmatix. The other authors have no conflicts of interest to declare. NA.

Infertile patients with inflammatory bowel disease have comparable in vitro fertilization clinical outcomes to the general infertile population

To assess clinical outcomes of females diagnosed with Inflammatory Bowel Disease (IBD) and infertility, which underwent in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy. (PGT-A). Retrospective cohort study comparing clinical outcomes of patients with Inflammatory bowel disease who underwent IVF with PGT-A with a subsequent euploid single embryo transfer (SET) against a matched control group. Thirty-eight patients with an IBD diagnosis were compared to 114 controls. There was no significant difference in cycle outcomes among IBD and Control cohorts [implantation rate (71.0% vs. 78.0% (p = .68)], clinical pregnancy rate [50.0% vs. 60.5% (p = .68)], live birth [62.9% vs. 73.0% (p = .06)] multiple pregnancy rate [0% vs. 1.1% (p = .25)] and clinical pregnancy loss rate [10.5% vs. 5.7% (p = .54)]. An IBD diagnosis was not found to significantly modify the odds of implantation [adjusted OR = 0.6 (95% CI −1.2 to 0.8)]. Additionally, the odds of implantation in patients with IBD were not altered by having ulcerative colitis or Crohn’s disease diagnosis. (OR = 0.4 95% CI 0.1–1.9). Patients diagnosed with IBD who undergo a SET have clinical outcomes comparable to the general infertile population. Patients and physicians can be reassured that an IBD diagnosis does not impair IVF treatment outcomes.SYNOPSISInfertile patients with inflammatory bowel disease who utilized a single, euploid blastocyst transfer had IVF success rates comparable to the general infertile population.

Reproductive outcomes of IVF patients with unicornuate uteri

In this retrospective observational study, the pregnancy, perinatal and obstetric outcomes of patients diagnosed with unicornuate uteri were compared with those of patients with normal uteri after undergoing intracytoplasmic sperm injection (ICSI) with fresh and cryopreserved embryo transfer. From a select population of 9676 infertile patients receiving IVF treatment, 75 (0.78%) were diagnosed with unicornuate uteri between January 2009 and December 2015. Fifty of them underwent ICSI treatment, with 90 fresh and cryopreserved embryo transfers. No significant differences were found between the biochemical, clinical and implantation rates of the first treatment cycles of the two groups; the ongoing pregnancy rate was significantly lower (P = 0.042; 34.0 versus 53.0%) in the unicornis group, as the result of a clinically higher clinical pregnancy loss rates (22.0 versus 15.9%). Twenty-three clinical pregnancies resulted from the 50 first treatment cycles in the unicornis group, resulting in 14 live births, one ongoing pregnancy, five miscarriages, one ectopic pregnancy and two terminations. The 14 live births were delivered at 35.9 gestational weeks, with seven preterm (<37 weeks) and four low birth weight deliveries. Patients with unicornuate uteri are at increased risk of miscarriage, preterm delivery, low birth weight delivery and reduced live birth rates.

A Comparison of Pattern of Pregnancy Loss in Women with Infertility Undergoing IVF and Women with Unexplained Recurrent Miscarriages Who Conceive Spontaneously.

Objective. Women with infertility and recurrent miscarriages may have an overlapping etiology. The aim of this study was to compare the pregnancy loss in pregnancies after IVF treatment with spontaneous pregnancies in women with recurrent miscarriages and to assess differences related to cause of infertility. Methods. The outcome from 1220 IVF pregnancies (Group I) was compared with 611 spontaneous pregnancies (Group II) in women with recurrent miscarriages. Subgroup analysis was performed in Group I based on cause of infertility: tubal factor (392 pregnancies); male factor (610 pregnancies); and unexplained infertility (218 pregnancies). Results. The clinical pregnancy loss rate in Group I (14.3%) was significantly lower than that of Group II (25.8%, p < 0.001) and this was independent of the cause of infertility. However the timing of pregnancy loss was similar between Groups I and II. The clinical pregnancy loss rate in Group I was similar in different causes of infertility. Conclusions. The clinical pregnancy loss rate following IVF treatment is lower than that of women with unexplained recurrent miscarriages who conceived spontaneously. This difference persists whether the infertility is secondary to tubal factors, male factors, or unexplained cause.

Early clinical pregnancy loss rate in poor responder patients does not change compared to age-matched normoresponders

To investigate the early clinical pregnancy loss rate (ECPLR) of singleton gestations in poor responder (PR) patients. A retrospective study. Private assisted reproductive technology center. A total of 2,157 singleton clinical pregnancies were identified, 195 from PR and 1,962 from normoresponder (NR) patients. Poor response was accepted as retrieval of four or fewer oocytes. Patients who yielded more than five oocytes were accepted as NR control group. Patients were age stratified as <or=35, 36-39, and >or=40 years. Comparative evaluation of ECPLR in PR and NR patients according to age. Out of 195 singleton clinical pregnancies achieved in poor responders, 31% resulted in early clinical pregnancy loss; ECPLR were 22%, 32%, and 59% in the <or=35, 36-39, and >or=40 year age groups, respectively. When ECPLR in singleton gestations of PR patients was compared with that of NR patients according to age, no significant differences were found for all age groups. Early clinical pregnancy loss rate was not found to differ significantly between PR and NR patients at all age groups. Therefore, PR patients should be counseled about their lower probability of clinical pregnancy but similar ECPLR compared with their age-matched NR counterparts.

A comparative analysis of embryos derived from routine in-vitro fertilization and subzonal microinsemination

Embryos obtained from patients undergoing routine in-vitro fertilization (IVF) and embryo transfer were compared with those undergoing subzonal microinsemination (SUZI) for male factor infertility. Overall, the proportion of cleaved embryos was significantly higher in the IVF group in comparison with the SUZI group at 48 h post-insemination [1533 out of 1609 (95.3%) versus 776 out of 952 (81.5%)]. The mean +/- SD grading score of the IVF-derived embryos of 3.61 +/- 0.50 was significantly better than that for SUZI of 2.97 +/- 0.86 (P < 0.0005) at the same time. The implantation rates following the replacement of IVF or SUZI embryos at 48 h were comparable: 14.3 and 10.0% respectively. However, the IVF embryo implantation rate of 15.1% at 72 h was significantly better than that following the replacement of SUZI embryos at either 48 (10.0%) or 72 h (8.0%). The replacement of SUZI-derived embryos at 48 h resulted in significantly higher pregnancy (25.0%) and implantation rates (10.0%) than at 72 h, with rates of 10.8 and 8.0% respectively. Similarly, the overall embryo quality deteriorated following in-vitro culture for up to 72 h. The clinical pregnancy loss rate (33.0%) was highest following the replacement of SUZI embryos at 72 h, although the data were limited. It is suggested that these data indicate that a combination of in-vitro manipulation, the injection of multiple spermatozoa into the subzonal space and probably the genomic capacity of spermatozoa derived from poor-quality semen may contribute to the poorer outcome of embryo development following SUZI. Prolonged in-vitro culture beyond 48 h appears to be deleterious to the development of SUZI cleaved embryos and the subsequent outcome of treatment, and hence should be avoided.