Number Of Transferred Embryos Research Articles

Correlation of female age with outcome of IVF in a low-resource setting.

To determine the effect of female age on pregnancy outcome after in vitro fertilization/embryo transfer (IVF-ET). A prospective study was conducted involving 266 women who had IVF-ET at Nisa Fertility and Genetic Center, Abuja, Nigeria. All eligible consenting women were recruited to the study. The main outcome measure was clinical pregnancy. Data were analyzed using IBM SPSS Statistics version 25. P< 0.05 at 95% confidence intervals was taken as significant. A total of 266 patients were recruited and included in the study; 104 pregnancies were recorded, giving an overall pregnancy rate of 39.1%. The age range of the patient was 26-43 years (mean age 33.9± 2.41 years) while the mean number of embryo transfers per patient was 2.2. The clinical pregnancy rate for women aged below 30 years was 69.4% while the pregnancy rate for patients aged 30-34 years, 35-39 years, and 40-43 years was 52.6%, 24.7%, and 9.4%, respectively (P< 0.0001). The study found that the success rate of IVF-ET decreases significantly in women aged over 34 years. Women should be counseled about the age-related risk of infertility and referred to a fertility center as early as possible.

8999 Reproductive Outcomes and Overall Prognosis of Patients with Asherman's Syndrome Undergoing IVF Cycles

<h3>Study Objective</h3> To estimate the impact of Asherman's Syndrome (AS) following hysteroscopic adhesiolysis on short term reproductive outcomes and the time to achieve pregnancy in infertile patients during IVF cycles. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Tertiary university affiliated medical center. <h3>Patients or Participants</h3> Fifty-one infertile patients who were treated for Asherman's syndrome (AS) and underwent IVF cycles (study group). Patients were matched with controls in a 1:1 ratio, according to their age and etiology of infertility (control group). <h3>Interventions</h3> The collected date was obtained from medical records and telephonic survey. <h3>Measurements and Main Results</h3> There was no difference in the mean number of embryo transfer per patient between the two groups (4.9 ±4.6 vs. 6.22 ±4.3, p=0.78). The mean endometrial thickness before embryo transfer was significantly higher among women in the control group (8.7 ±1.8 vs. 6.95±1.7, respectively, p=0.001). Women with AS had significantly lower cumulative live birth rate and significantly higher miscarriage rate as compared to women in the control group (23.5% vs 56.8, p=0.001 and 41% vs. 15.6%, p=0.008 accordingly). The mean endometrial thickness was significantly higher among women with AS who had live birth (8.2 (±1.4) 6.9 (±1.2), p=0.001). The Overall time to conception was significantly longer among with AS (407.962 ±74.7 Vs 785.6 <h3>Conclusion</h3> AS has an impact on the reproductive potential in infertile patients following hysteroscopic adhesiolysis. Endometrial thickness was shown to be an important predictor for live birth among women with AS that utilizing IVF.

Efecto de la abstinencia sexual masculina en los resultados reproductivos

Background and objectiveThe available literature suggests that longer periods of male abstinence have a negative effect on reproductive outcomes. However, the low sample size of the available studies and the lack of consensus make further research necessary in order to establish an optimal abstinence period to improve the reproductive possibilities of each couple. The aim of this study was to estimate the influence of male sexual abstinence period on reproductive outcomes after IVF and ICSI. Material and methodsThis retrospective, observational, multicentre, cohort study has the largest sample size to date, 7789 embryo transfers were included in the study. The study participants were divided into 4 quartiles according to their period of abstinence: Q1 (0–3 days abstinence), Q2 (3–4 days), Q3 (4–5 days) and Q4 (>5 days abstinence). The outcome measures used were: gestation rate (biochemical, clinical and evolutionary), VUR delivery rate and miscarriage rate (biochemical and clinical) calculated per single embryo transfer and for the total number of embryo transfers for each patient. ResultsBiochemical gestation rate (adjusted Odds Ratio (ORadj): 2.943, p = .022), clinical gestation rate (ORajd: 2.649, p = .028), evolutionary gestation rate (ORadj: 3.637, p = .005) and VUR delivery rate (ORadj: 3.008, p = .021) were significantly higher in the third quartile when compared to the first quartile. Clinical gestation (ORadj: 0.192, p = .010) was significantly lower in the fourth quartile when compared to the first quartile. ConclusionsA period of sexual abstinence of more than 4 and up to 5 days significantly increases biochemical, clinical and evolutionary gestation rates and VUR delivery rate. A period of abstinence longer than 5 days appears to worsen reproductive outcomes.

Sperm DNA fragmentation negatively influences the cumulative live birth rate in the intracytoplasmic sperm injection cycles of couples with unexplained infertility.

ObjectiveThis study aimed to determine the effect of sperm DNA fragmentation (SDF) on the cumulative live birth rate (CLBR) in intracytoplasmic sperm injection (ICSI) cycles in couples with unexplained infertility.MethodsWe conducted a prospective study of 145 couples who underwent ICSI cycles for unexplained infertility. Based on the SDF rate, patients were categorized into a low SDF group (SDF ≤30%, n=97) and a high SDF group (SDF >30%, n=48). SDF was assessed using the acridine orange test on density gradient centrifugation prepared samples. The CLBR was calculated as the first live birth event per woman per egg collection over 2 years.ResultsThe high SDF group (SDF >30%) showed a significantly lower CLBR (p<0.05) and a significantly higher miscarriage rate (p<0.05) than the low SDF group (SDF ≤30%). No significant difference was observed in the implantation and cumulative pregnancy rates between the two SDF groups. The total number of embryo transfers was stratified further into fresh and frozen embryo transfers. In the fresh embryo transfers, there were significant differences in the implantation rates, clinical pregnancy rates, and live birth rates (p<0.05) between the low SDF and high SDF groups. However, in the frozen embryo transfers, there were no significant differences in clinical outcomes between the two groups. In the multivariable logistic regression analysis, SDF was a predictor of CLBR (p<0.05) when adjusted for possible confounding factors. ConclusionHigh SDF was associated with a lower CLBR and a higher miscarriage rate in the ICSI cycles of couples with unexplained infertility.

Association of the Number of Embryos Transferred with Ectopic Pregnancy after Embryo Transfer in Patients with Salpingectomy or Proximal Tubal Occlusion

Background: With the prevalence of assisted reproductive technology (ART), the incidence of ectopic pregnancy (EP) is increasing, especially in patients with salpingectomy or proximal tubal occlusion. Methods: A total of 11,609 women who were undergoing ART and had undergone salpingectomy or proximal tubal occlusion, and 5388 women who achieved a clinical pregnancy were included in the study. Statistical analysis was used to determine whether the number of embryos transferred was associated with EP. Results: Both the number of embryos transferred and the day of embryo transfer differed significantly between those with and without EP (p &lt; 0.05), while the number of embryos transferred was associated with interstitial pregnancy (IP) (p &lt; 0.05) in those undergoing frozen-thawed embryo transfer (ET) cycles. Following multivariate modeling, the odds of having an EP in women undergoing frozen-thawed ET cycles increased with the number of embryos transferred (odds ratio [OR] 2.003, 95% confidence interval [95% CI] 1.036–3.876). Conclusions: The embryo transfer number was considered a risk factor for EP in patients undergoing frozen-thawed ET who had undergone salpingectomy or proximal tubal occlusion.

Reproductive Outcomes and Overall Prognosis of Women with Asherman's Syndrome Undergoing IVF

To evaluate the impact of Asherman syndrome (AS) following hysteroscopic adhesiolysis on reproductive outcomes and the time to achieve pregnancy in women with infertility undergoing in vitro fertilization (IVF) treatment. Case-control study. Tertiary university-affiliated medical center. Fifty-one infertile women who were treated for AS and underwent IVF (study group) matched for age and etiology of infertility with non-AS controls at a 1:1 ratio. Medical records search, chart review, and phone survey were used to assess reproductive outcomes. A multivariate logistic regression analyses was used to assess live birth, accounting for patient age at stimulation cycle start, parity, number of embryos transferred, and endometrial thickness. A survival analysis was performed to assess the times that had lapsed from interventions to conception. The study group of 51 women included 38 (74.5%) with moderate to severe disease. The mean number of embryo transfers per woman was similar for the study and control groups (4.9 ± 4.6 vs 6.22 ± 4.3, respectively, p=.78). The controls had a significantly higher mean endometrial thickness before embryo transfer (8.7 ± 1.8 mm vs 6.95 ± 1.7 mm, p=.001). The overall time to achieve live birth was significantly longer in women with AS (p=.022). In a logistic regression analysis, the presence of moderate to severe AS was shown to be an independent factor for achieving a live birth (adjusted odds ratio 0.174, 95% confidence interval [CI], 0.032-0.955, p=.004). Women with AS who had live births had a significantly thicker mean endometrial thickness (8.2 ± 1.4 mm vs 6.9 ± 1.2, p=.001). Moderate and severe AS has a detrimental effect on reproductive performance in infertile women. Endometrial thickness is an important predictor for live births among women with AS who undergo IVF.

Are ovarian responses and the number of transferable embryos different in females and partners of male balanced translocation carriers?

To compare ovarian response and the number of transferable embryos between women with balanced autosomal translocations and women whose partners carry the translocation (control group). To investigate the predictive value of metaphase II (MII) oocyte number and biopsied embryo number for gaining at lowest one transferable embryo. We retrospectively analyzed 1942 preimplantation genetic testing for structural rearrangements (PGT-SR) cycles of 1505 balanced autosomal translocation couples over 8years. All cycles were divided into two subgroups: Robertsonian and reciprocal translocations (ROBT and ReBT). Receiver operator characteristic (ROC) curves were plotted to ascertain a cutoff of MII oocytes and biopsied embryos as predictors of gaining at lowest one transferable embryo. There were no statistical differences in baseline features or ovarian response indicators regarding the number of retrieved/MII oocytes, E2 level on the day of HCG, and ovarian sensitivity index (OSI) between women with balanced autosomal translocations and control group (P > 0.05). A decreased number of transferable embryos were found in women with balanced autosomal translocations regardless of the type of translocation. The cutoff values for gaining at lowest one transferable embryo are 12.5 MII oocytes and 4.5 biopsied embryos, respectively. Women with balanced autosomal translocations have a normal ovarian response, but fewer transferable embryos, meaning that higher gonadotropin (Gn) doses may be required to increase transferable embryos. When fewer than 12.5 MII oocytes or 4.5 blastocysts are obtained in a PGT-SR cycle, couples should be notified that the likelihood of gaining a transferable embryo is low.

The relationship between thyroid autoimmunity and poor response to ovarian stimulation in in vitro fertilization women with infertility.

Thyroid autoimmunity (TAI) is the most common autoimmune disorder. Patients with TAI are usually euthyroid, and the presence of anti-thyroid peroxidase (anti-TPO) in patients with or without thyroid dysfunction is associated with infertility, recurrent embryo implantation failure, and early pregnancy loss. We aimed to investigate the relationship between low ovarian reserve, pregnancy outcomes, and TAI. This retrospective cohort study was conducted in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients between 2010 and 2018. All patients (n = 1400) for whom thyroid autoantibody testing was requested were detected. A study group was formed from patients with anti-TPO positivity (n = 363). The control group (n = 555) comprised euthyroid anti-TPO negative patients matched to the study group regarding age and body mass index (BMI). Mean serum TSH value was 2.35 ± 1.70 mIU/mL in anti-TPO-positive patients and 1.81 ± 1.2 mIU/mL in controls, and the difference was significant (p < 0.05). Total dose of gonadotropins used in ovulation induction in anti-TPO-positive and control patients were 3000 IU and 2700 IU, respectively, and the difference was statistically significant (p < 0.05). The number of metaphase 2 oocytes was significantly lower in the anti-TPO-positive group (p < 0.05). Embryo transfer number and embryo grade were significantly lower in the anti-TPO-positive group (p < 0.01). Poor ovarian response was significantly higher in anti-TPO-positive patients (40%) as compared to anti-TPO-negative controls (30%) (p < 0.01). Clinical pregnancy rate was significantly lower in the anti-TPO-positive group (29.2%), as compared to the antibody-negative group (38.4%) (p < 0.01). There are controversial data regarding the impact of antithyroid antibodies on ovarian reserve and pregnancy outcome after IVF treatment. The results of this study indicate that there was a relationship between TAI and poor ovarian response, and that TAI adversely affects IVF outcomes. Further investigations are required to explore the mechanism behind these effects.

Bioactive supplements influencing bovine in vitro embryo development.

Ovum pickup and in vitro production (IVP) of bovine embryos are replacing traditional multiple ovulation embryo transfer (MOET) as the primary means for generating transferable embryos from genetically elite sires and dams. However, inefficiencies in the IVP process limit the opportunities to produce large numbers of transferable embryos. Also, the post-transfer competency of IVP embryos is inferior to embryos produced by artificial insemination or MOET. Numerous maternal, paternal, embryonic, and culture-related factors can have adverse effects on IVP success. This review will explore the various efforts made on describing how IVP embryo development and post-transfer competency may be improved by supplementing hormones, growth factors, cytokines, steroids and other bioactive factors found in the oviduct and uterus during early pregnancy. More than 40 of these factors, collectively termed as embryokines, are reviewed here. Several embryokines contain abilities to promote embryo development, including improving embryo survivability, improving blastomere cell numbers, and altering the distribution of blastomere cell types in blastocysts. A select few embryokines also can benefit pregnancy retention after IVP embryo transfer and improve neonatal calf health and performance, although very few embryokine-supplemented embryo transfer studies have been completed. Also, supplementing several embryokines at the same time holds promise for improving IVP embryo development and competency. However, more work is needed to explore the post-transfer consequences of adding these putative embryokines for any adverse outcomes, such as large offspring syndrome and poor postnatal health, and to specify the specific embryokine combinations that will best represent the ideal conditions found in the oviduct and uterus.

O-291 Cumulative pregnancy rates of two strategies: day 3 fresh embryo transfer followed by day 3 or day 5 frozen embryo transfer, a Randomized Controlled Trial

Abstract Study question Are cumulative pregnancy rates different if supernumerary embryos are vitrified on day 5 instead of day 3? Summary answer Results do not show a significant difference in cumulative pregnancy rates between the vitrification day 3 and day 5 group. What is known already The pregnancy and live birth rates following IVF or ICSI treatment are higher after extended embryo culture and blastocyst transfer (day 5) compared to cleavage-stage (day 3) embryo transfer (Glujovski et al 2016). Cumulative pregnancy rates after fresh and frozen embryo transfers show no significant difference after one oocyte retrieval (OR) but only one study used vitrification for the cryopreservation of supernumerary embryos while four studies used a slow freezing protocol (Fernandez-Shaw et al., 2014). A retrospective analysis by De Vos et al., 2016 concluded significantly less embryo transfers were necessary until live birth for blastocyst-stage embryos. Study design, size, duration A Randomized Controlled Trial was performed in an academic center between 01/01/2018 and 31/07/2020. Patients were randomized in the vitrification day 3 or day 5 group. Primary outcome is the number of embryo transfers needed to reach ongoing pregnancy. Power calculation revealed that 75 patients were needed in each group, assuming a median of 4 transfers in the day 3 group versus a median of 2 transfers in the day 5 group to achieve pregnancy. Participants/materials, setting, methods Patients &amp;lt;38 years undergoing their first/second OR were randomized at the start of the cycle. Embryos with ≥6 cells, &amp;lt;25% fragmentation and equal blastomeres and blastocysts with expansion grade ≥2 with inner cell mass and trophectoderm score A/B were vitrified. A time-to-event analysis was performed with ongoing pregnancy as the event of interest and the number of embryo transfers as the time component. The statistical comparison was performed by a Cox proportional hazards model. Main results and the role of chance By December 2021, 234 transfers (96 fresh and 138 frozen) of 78 patients were performed in the vitrification day 3 group and 207 transfers (83 fresh and 113 frozen) of 80 patients in the vitrification day 5 group. The time-to-event analysis did not show a difference between both arms with regards to ongoing pregnancy as the primary study outcome (HR 1.25, 95% CI 0.81; 1.91, p = 0.31). The cumulative ongoing pregnancy rate after 8 transfers was 56% in the day 3 group versus 57% in the day 5 group. Median number of transfers till pregnancy was 6 versus 4, respectively. Similar results were found for the secondary study outcome (clinical pregnancy with fetal heart rate, HR 1.19, 95% CI 0.80; 1.80, p = 0.407). A total of 225 transfers (93 fresh and 132 frozen) of 78 patients were performed in the vitrification day 3 group and 201 transfers (92 fresh and 109 frozen) in the vitrification day 5 group. The cumulative clinical pregnancy rate after 8 transfers was 62% in the day 3 group versus 59% in the day 5 group. Median number of transfers till pregnancy was 6 versus 4, respectively. Limitations, reasons for caution Although power calculation revealed 75 patients are needed in each study group (β = 0.87, α &amp;lt; 0.05), numbers remain low. Wider implications of the findings A recent systematic review and cumulative meta-analysis of Marconi et al. (2021) suggests day 5 embryo transfer is associated with higher risk of preterm birth although evidence was low. Health/economic analyses should be taken into account to determine the most cost-effective strategy for patient and hospital/society. Trial registration number NCT04196036

P-557 Fresh Transfer with Supernumerary PGT-A Biopsy: The Best of Both Worlds

Abstract Study question What is difference in time to pregnancy for patients between 35-40 years who undergo fresh versus frozen-thawed embryo transfers with or without PGT-A? Summary answer Patients undergoing fresh embryo transfer (ET) had a shorter time to pregnancy within the same cycle compared to patients electing for freeze-all cycles. What is known already When comparing clinical pregnancy rates following fresh versus frozen-thawed embryo transfers, multiple studies have shown a higher clinical pregnancy rate among frozen-thawed embryo transfers compared to fresh embryo transfers. Particularly for patients over 35 years, there has been a growing national trend towards elective freeze-all cycles, for reasons such as to pursue preimplantation genetic testing for aneuploidy (PGT-A). While PGT-A testing can be effective in reducing miscarriage in patients age 38-40, there is limited studies evaluating time to pregnancy within this population, especially in the context of each passing month’s effect on fertility. Study design, size, duration Retrospective review was performed for 697 IVF cycles and 881 transfers from January 2016 – December 2021 at a single academic fertility center in Boston, Massachusetts. Two-tailed t-tests and analysis of variance (ANOVA) were used to compare differences, with p-value less than 0.05 set for statistical significance. All PGT-A testing as performed using a modified FAST-SeqS next generation sequencing method (Invitae, San Francisco, CA). Participants/materials, setting, methods Cycle characteristic of patients between 35-40 were categorized to four groups: Fresh ET with PGT-A of supernumerary embryos (82 transfers), Fresh ET without PGT-A (526 transfers), Freeze-all cycle with PGT-A (223 transfers), and Freeze-all cycle without PGT-A (50 transfers). All averages were calculated within one IVF cycle with a single cohort of embryos. Time to pregnancy was calculated in days from day of retrieval to positive serum beta-human chorionic gonadotropin (bHCG). Main results and the role of chance Among the 881 transfers, 478 had fresh ETs and 403 had frozen-thawed ETs with or without PGT-A respectively. When comparing fresh and freeze-all cycles, there was no difference in average numbers of transfers performed to achieve a clinical pregnancy (1.27 fresh vs 1.25 freeze-all, p = 0.56). For patients who didn’t elect for PGT-A, there was no difference in number of embryos transferred (1.86 for fresh versus 2.06 for freeze-all, p = 0.54). For patients who elected for PGT-A, the average number of embryos transferred was higher for patients that opted for fresh transfer over freeze-all (1.67 for fresh ET with PGT-A of supernumerary embryos versus 1.24 for freeze-all PGT-A, p = 0.0025). Average days from oocyte retrieval to pregnancy was significantly lower for all fresh ETs (28.8 days for fresh ET without biopsy, 26.6 days for fresh ET with biopsy of supernumerary embryos, p &amp;lt; 0.0001) compared to all freeze-all transfers (110.9 days for freeze-all ET without biopsy, 119.5 days for freeze-all ET with biopsy, p &amp;lt; 0.0001). This delay in time to pregnancy is partially attributed to pending genetic testing results, however, these results usually return in 2-3 weeks, which does not account for the near 3-month delay in time to pregnancy among freeze-all cycles. Limitations, reasons for caution These retrospective findings were of all women who achieved pregnancy from one retrieval. These results are not reflective of the patients who needed to undergo multiple cycles to achieve pregnancy, or patients who never achieved pregnancy. Wider implications of the findings These findings suggest that PGT-A may be offered to patients &amp;gt; 35 to minimize the number of embryos for transfer. Patients opting for a fresh transfer of an untested embryo and biopsy of supernumerary embryos had a nearly 3-month shorter time to pregnancy than those electing for a freeze-all cycle Trial registration number not applicable

P-737 Optimization of the multistep embryo transfer cycles in assisted reproductive technologies (ART) treatments

Abstract Study question Decision of how many and which embryos to transfer in each cycle is determined by multiple factors, and the integration of patient-specific considerations is challenging. Summary answer We developed an embryo transfer strategy support tool (ET-SST) that finds the optimal way to conduct the embryo transfer process. What is known already In each transfer cycle, a decision of how many and which embryos to transfer is determined, based on embryo quality, risk of multiple pregnancies, maternal prognosis, cryopreservation factor, and the cost of each cycle. The parameters can be conflicting, high maternal receptivity might encourage single embryo transfer (SET) yet poor embryo quality might encourage multiple embryos transfer (MET) while co-considering cryopreservation, clinical risks, and future possible transfer. Current guidelines are not case-specific and only dictate a limit on the number of embryos to transfer based on maternal age solely, without regarding the heterogeneity of patients and several transfer cycles. Study design, size, duration We created a computational model integrating multiple parameters, assigning a specific embryo transfer option a value, based on the expected pregnancy rate. Assuming a given number of transferable embryos in a cycle, we calculate the expected value of a series of transfers (a strategy), using a recurrence relation. We applied dynamic programing that efficiently identifies the optimal strategy for the given cycle while considering maternal and other clinical parameters incorporated into the equation. Participants/materials, setting, methods The number of possible strategies is exponential with the number of embryos. There are 70 strategies with only four embryos viable to transfer, and the number increases to 4,550 with six embryos and over 100,000 with eight embryos. We created a recursive relation that describes the value of each strategy. Evaluating the different strategies is challenging even for modern computers. We apply dynamic programming to efficiently solve the recursion relation and identify the optimal strategy. Main results and the role of chance To assess the optimal transfer strategies, we developed the ET-SST and generated an online web application (https://etsst.researchsoftwarehosting.org/). For a given set of oocyte retrieval embryos, the ET-SST calculates all possible multistep embryo transfer strategies and, using the value function, finds the optimal strategy based on embryonic, maternal, and clinical user-input factors. (1) Embryo quality scores (using any method of choice). (2) Maternal prognosis score (endometrial receptivity, maternal age). (3) Multiple pregnancy score. (4) Cryopreservation factor (estimating the effects of embryo freeze-thaw procedure). (5) Transfer cycle cost. Each factor receives a value between 0 (non-favorable) and 1 (favorable). Based on these parameters, the ET-SST defines the optimal strategy that maximizes the value function. To avoid limitations on the assessment of the embryos' developmental potential and the patients' clinical prognosis, the ET-SST allows using all tools of choice for the user-input assignment. Limitations, reasons for caution This newly developed computerized model was not yet tested in a randomized trial. Wider implications of the findings Here we showed an algorithm that generates a case-specific strategy that can incorporate the clinical parameters that can be evaluated by any method that is preferred by the clinician. The modern evidence-based IVF clinic should include not only evidence-based clinical parameters but also algorithm-guided personalized decision making. Trial registration number exempted

P-755 Conventional outcome reporting per embryo-transfer cycle systematically underestimates the chance of success of women undergoing ART: a source of bias in registries, trials and guidelines

Abstract Study question How should ART treatment success be estimated from data consisting of several treatment attempts per subject (e.g., fresh transfer followed by cryotransfer[s] and/or repetitive attempts)? Summary answer Live birth rate estimates per transfer cycle will be substantially higher when accounting for differences in the number of embryo transfers between subjects. What is known already Preconception counselling and expectation management is an integral part of fertility care. In the course of IVF-treatment, the majority of women undergo several embryo transfers (ET). The live birth rate per ET cycle may be severely underestimated since women with a poor prognosis will be overrepresented in the population compared to women with a good prognosis. This is because women achieving a live birth early will contribute few ETs, whereas women without live births will contribute several ETs to the pool of observations. This phenomenon does also add bias when comparing the live birth rates between fresh- transfers and cryo-transfers. Study design, size, duration The complete data set from the RAINBOW trial (NCT03564509) was applied to exemplify the underestimation of live birth chance of individual women in cryo-cycles. In total 557 women underwent treatment in a fixed, individualized daily- dose of follitropin delta in a long GnRH agonist protocol, IVF/ICSI and blastocyst transfer. Surplus blastocysts were cryopreserved on day 5/6 and subsequently used for cryo-transfers up to one year after start of the stimulation. Participants/materials, setting, methods Live birth rate was analyzed using a mixed effect logistic regression model where the log-odds of achieving a live birth was assumed to be normally distributed in the trial population. Type of transfer (fresh or cryo) was included as a factor in the model. The delta method was used to transform estimated mean log-odds from the model into estimated live birth rates per transfer, and to estimate the difference between fresh- and cryo-transfers. Main results and the role of chance Of the 619 women starting stimulation, 557 had at least one fresh- or cryo-transfer. A total of 927 embryo transfers were performed whereof 520 fresh- and 407 cryo-transfers. In total, 252 subjects had at least one cryotransfer, 102 had a second cryotransfer, 37 a third, 12 a fourth, three a fifth, and one had a sixth cryotransfer, respectively. Of the 520 fresh transfers, 212 (41%) resulted in a live birth, whereas for the 407 cryo-transfers 100 (25%) resulted in a live birth (unadjusted difference 16%). When using the mixed effect logistic regression model to adjust for repeated transfers in the same women, the live birth rates were estimated to be 41% for fresh transfers and 36% per transfer for cryo-transfers. The difference between rates for fresh transfer and per cryo-transfer was estimated to be 5.3% with 95% confidence interval ranging from -6.6% to 17.1% and with no statistically significant difference (p = 0.3827). Limitations, reasons for caution Comparison between live birth rate after fresh transfer and per cryotransfer in the same group of women will already be biased in favour of the fresh transfer. This is because the fresh transfer will normally use the embryo of highest quality, leaving embryos of lower quality for cryo-transfers. Wider implications of the findings Average chance of success reported per cycle or per embryo-transfer (e.g. registry reports) do not apply to individual couples, especially not at the outset of treatment. Live birth rates per transfer from datasets encompassing multiple transfers from single individuals can be more accurately reported using mixed effect logistic regression models. Trial registration number NCT03564509

Heterotopic Pregnancy Secondary to in vitro Fertilization-Embryo Transfer: Risk Factors and Pregnancy Outcomes.

BackgroundWith the widespread application of assisted reproduction technology (ART) and increased pelvic inflammatory disease, the incidence of heterotopic pregnancy (HP) has risen. However, the risk factors and treatment of HP remain indefinite.ObjectivesTo explore risk factors affecting the incidence of HP secondary to in vitro fertilization-embryo transfer (IVF-ET) and pregnancy outcomes after surgical treatment of HP.Methods29 patients with HP and 116 with an intrauterine-only pregnancy (IUP) after IVF-ET during the same period were included retrospectively from January 2015 to September 2020.ResultsPatients with HP had a higher proportion of previous ectopic pregnancies, multiple abortion history (≧2 times) and tubal indication for IVF than IUP. Besides, they had a greater possibility to end in spontaneous abortion (31.03 vs.13.79%, P = 0.028) and preterm delivery (25.00 vs. 7.00%, P = 0.035), less possibility to result in a live birth (58.62 vs. 78.45%, P = 0.028). History of multiple abortions (≥2 times) [odds ratio (OR) 3.031, 95% confidence intervals (CI) 1.087–8.453; P = 0.034], tubal infertility (OR 3.844, 95% CI 1.268–11.656; P = 0.017), previous ectopic pregnancies (OR 2.303, 95% CI 0.625–8.490; P = 0.021) and number of embryo transfer (OR 0.300, 95% CI 0.092–0.983; P = 0.037) resulted in an elevated proportion of HP in IVF treatment. Shorter operative duration, smaller size of the ectopic mass and location in the ampulla of the fallopian tube were associated with higher chance of survival in the coexistent intrauterine pregnancy after surgical treatment.ConclusionsPrevious history of ectopic pregnancy, multiple abortions, tubal infertility and multiple-embryo transfer may be considered as meaningful risk factors of subsequent HP following IVF-ET. In patients with HP treated by surgery, shorter operative duration, smaller size of the ectopic mass and location in the ampulla of the fallopian tube means better reproductive prognosis.

Different actors for the same play: the impact of the embryologist performing the embryo transfer

Research questionDoes the embryologist performing the embryo transfer impact the cycle outcome, in terms of ongoing pregnancy rate (OPR)? DesignThis single-centre retrospective study analysed the results, corrected for main confounders, from 28 embryologists and 32 physicians who performed respectively 24,992 and 24,669 fresh embryo transfers (either at cleavage or blastocyst stage) during a 20-year period from January 2000 to December 2019, in a university-affiliated tertiary care assisted reproductive technology (ART) centre. Primary outcome was OPR, defined as the number of viable pregnancies that had completed at least 12 weeks of gestation on the total number of embryo transfers performed. The study also assessed whether the embryologist's experience, measured in terms of number of embryo transfers performed prior to the day of the procedure, had an impact on their performance. The secondary aim was to assess which variable, between the embryologist and physician, more significantly impacted OPR. ResultsThe overall unadjusted OPR was 22.54%. The embryologist performing the embryo transfer was found to significantly affect the OPR (P < 0.0001), corrected for potential confounders. However, the physician factor made a slightly greater contribution to the model (likelihood ratio 21.86, P < 0.001 versus likelihood ratio 17.20, P < 0.0001). No significant association was found between the experience of the embryologist and OPR (P = 0.067). ConclusionsThese results show how the ‘human factor’ influences the chances of a positive outcome in the final step of a high-tech procedure and underline the importance of implementing an operator quality performance programme (both for physicians and embryologists) to ensure the maintenance of benchmark results and eventually retrain underperforming operators.

Sperm deoxyribonucleic acid fragmentation (by terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay) does not impair reproductive success measured as cumulative live birth rates per donor metaphase II oocyte used

To better study the effect of sperm deoxyribonucleic acid fragmentation (SDF) on intracytoplasmic sperm injection (ICSI) outcomes from an ovum donation program by assessing the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbR), and metaphase II (MII) oocytes required in consecutive treatments to achieve the first newborn. A multicenter retrospective cohort study was conducted, and the Kaplan-Meier survival curves were generated to calculate the CLBR with regard to the SDF degree. Private university-affiliated invitro fertilization centers. Data from 864 couples using donated eggs and undergoing ICSI from 2000 to 2019 were analyzed. Sperm deoxyribonucleic acid fragmentation was measured using terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay on their ejaculated sperm. None. Live birth rate (LBR) per first ET and per all consecutive ETs within the same patient and CLBR per ET, per EmbR, and per MII oocyte used considering the SDF level. A total of 1,903 ICSI cycles were considered, encompassing 6,340 donated oocytes, 2,543 embryos, and 1,145 ETs. Comparing ≤15% SDF (low) with >15% SDF (high) or by 10% SDF ranges, the LBRs per first ET and per all ETs did not significantly differ. The Kaplan-Meier curves of the CLBR per ET, per EmbR, and per donor oocyte consumed were similar between the SDF groups evaluated. Elevated SDF does not reduce the LBR or cumulative probability to obtain a child when calculated per ET, per EmbR, and per donated MII oocyte used in couples undergoing ICSI cycles.

Combining PGT-A with PGT-M risks trying to do too much.

The primary objective of preimplantation genetic testing for monogenic disorders (PGT-M) is to avoid having a child with a serious monogenic disease. Combining testing for unrelated sporadic chromosomal abnormalities (PGT-A) and excluding embryos with chromosomally abnormal results from transfer proffers the chance to mitigate the risk of miscarriage and to reduce the number of embryo transfers, but also risks excluding healthy embryos from transfer due to abnormal test results that do not reflect the true potential of the embryo. The theoretical utility of combining PGT-M with PGT-A is explored in this communication. It is concluded that PGT-M without PGT-A is preferred to achieve an unaffected live birth. Since PGT-M is mostly undertaken by couples where the female partner is younger than 35years, PGT-A is likely to marginally mitigate the risk of miscarriage. Experimental non-selection studies are needed to assess the potential detrimental effect of combining PGT-M with PGT-A in a clinical setting.

Association Between Fresh Embryo Transfers and Frozen-Thawed Embryo Transfers Regarding Live Birth Rates Among Women Undergoing Long Gonadotropin-Releasing Hormone Antagonist Protocols.

Background: The availability and use of frozen–thawed embryos after controlled ovarian hyperstimulation for assisted reproduction have increased with improvements in vitrification techniques and the rise of gonadotropin-releasing hormone (GnRH) antagonist protocols. Although evidence has shown that frozen–thawed embryo transfers (FETs) result in higher live birth rates than fresh embryo transfers, it is uncertain whether this association exists in cycles employing the GnRH antagonist protocol. Objective: To test the hypothesis that FETs are more likely to result in a live birth than fresh embryo transfers in a GnRH antagonist protocol cycle and to investigate whether frozen blastocyst transfer increases live birth rates compared to fresh blastocyst transfer. Design: A retrospective historical cohort study was conducted using data collected from the Department of Reproductive Medicine of Liuzhou Maternity and Child Healthcare Hospital for 1,437 patients who underwent the GnRH antagonist protocol between 1 January 2015, and 31 December 2020. The primary outcome was the live birth rate, which was compared between fresh embryo transfer and FET, and the secondary outcomes were clinical pregnancy rate and miscarriage rate, which were compared between the two groups. Analyses were adjusted to account for the age of the patient, number of embryo transfers, day of embryo transfer, and type of infertility. Results: Fresh embryo transfers accounted for 1,026 (71.4%) of the 1,437 patients who underwent the GnRH antagonist protocol in our analysis, while FETs accounted for 411 (28.6%). Patients with fresh and frozen–thawed embryos had comparable median body mass index (body mass index; 22.3 [IQR, 24.6–20.0] vs. 22.0 [IQR, 24.5–19.9]). There was a significant difference in the median age of the fresh embryo transfer group (34.0 [IQR, 39.0–30.0]) and the Frozen–thawed embryo transfer group (32.0 [IQR, 37.0–29.0]). Blastocysts were transferred in 14.6% of the fresh embryo transfer cycles and 45.5% of the FET cycles, whereas they account for 10.4% and 13.0% of all patients, respectively. The mean number of embryos transferred was 2 (IQR, 2.0–1.0) for the fresh embryo transfer group and 1 (IQR, 2.0–1.0) for the FET group, with a significant difference in the mean number of embryos transferred. The live birth rate after fresh embryo transfer vs. FET was 28.7% vs. 34.5% (absolute difference, 5.9%; adjusted relative risk [aRR], 1.15 [95% CI, 0.88–1.51]). The clinical pregnancy rates were 39.9% vs. 46.0%, respectively (absolute difference, 6.1%; aRR, 1.10 [95% CI, 0.85–1.43]). The miscarriage rates were 22.5% vs. 23.8%, respectively (absolute difference, 1.3%; aRR, 1.13 [95% CI, 0.75–1.70]). Conclusion: In this retrospective study of women who underwent assisted reproduction using GnRH antagonists, FETs resulted in a higher live birth rates and clinical pregnancy rates than fresh embryo transfers, which parts of these differences were attributable to embryo stage. However, the interpretation of the findings is limited by the possibility of selection and confounding biases.

MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study

BackgroundWhether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET).MethodsThis is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes.ResultsThere is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction<0.05). MTHFR 677TT homozygous mutation was found to impact reproductive outcomes under GnRHa short protocol but not GnRHa long protocol. MTHFR 677TT is significantly associated with decreased number of transferable embryos (p-value=0.028), decreased number of good-quality embryos (p-value=0.005), and decreased cumulative live birth rate (p-value=0.024) in patients undergoing GnRHa short protocol. However, the clinical pregnancy rate, miscarriage rate and live birth rate at the first embryo transfer cycle were not significantly different between the groups under both protocols (p-values>0.05).ConclusionsMTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.

IVF/ICSI cumulative live birth rates per consumed oocyte remain comparable regardless of sperm DNA fragmentation by TUNEL

Research questionDoes sperm DNA fragmentation (SDF) affect reproductive success of IVF and intracytoplasmic sperm injection (ICSI) cycles measured as cumulative live birth rates (CLBR) in unselected couples? DesignClinical data from 1339 couples undergoing 2759 IVF/ICSI cycles using autologous oocytes with a SDF test by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) assay on their ejaculated spermatozoa were retrospectively evaluated. Main outcomes were calculated according to two different analyses: using 15% SDF as cut-off point (low ≤15% and high >15%); and categorizing participants based on four SDF ranges (<10%, 10– <20%, 20–30% and >30%). Live birth rate and CLBR per number of embryo transfers, per number of embryos replaced and consumed oocytes required to achieve the first live birth according to level of SDF were the main outcomes assessed. ResultsNo significant difference was found in clinical pregnancy rate and miscarriage rate between both groups. No differences in LBR per embryo transfer were found for the first or for all embryo transfers when comparing ≤15% and >15% sperm DNA fragmentation or by SDF ranges. The CLBR according to the number of embryo transfers and the number of embryos replaced showed no statistically significant differences between different SDF groups. When the same number of oocytes were inseminated, similar CLBR were obtained regardless of the degree of male sperm DNA fragmentation. ConclusionsHigh SDF did not impair live birth rates of unselected males undergoing IVF/ICSI cycles with autologous oocytes per transfer or the cumulative probability of a live birth.