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Objective: To present a definition of recurrent implantation failure that accounts for the effects of female age and anticipated blastocyst euploidy rates on cumulative implantation rates., Design: Mathematical modeling., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): Mathematical modeling of cumulative implantation probability on the basis of published blastocyst euploidy rates across categories of female age., Main Outcome Measure(s): The number of blastocysts required to achieve 95% cumulative implantation probability under the assumption of the absence of any other factor affecting implantation., Result(s): When the euploidy status of the transferred embryo is unknown (i.e., not subjected to preimplantation genetic testing for aneuploidies), our simulation shows that no age category reaches 95% cumulative probability of implantation of at least one embryo until after transfer of seven blastocysts. The number of blastocysts required to reach the same threshold is higher for older patients. For example, women older than 38 years require transfer of more than 10 untested blastocysts for the upper range of predictive probability to meet the threshold of 95%. On the other hand, if the implantation rate for a euploid blastocyst is assumed to be 55%, then 4 blastocysts are enough to reach a cumulative probability rate greater than 95%, regardless of age., Conclusion(s): The term "recurrent implantation failure" should be a functional term guiding further management. We suggest that recurrent implantation failure should not be called until implantation failure becomes reasonably likely to be caused by factors other than embryo aneuploidy, the leading cause of implantation failure. We propose a new definition that factors in anticipated blastocyst euploidy rates across categories of female age, euploid blastocyst implantation rate, and a specified threshold of cumulative probability of implantation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the predictive value of endometrial thickness (EMT) for live birth when a lower threshold of EMT is not employed for embryo transfer (ET)., Design: Retrospective study SETTING: Academic assisted reproduction center PATIENT(S): All women who underwent fresh or frozen-thawed ET at the Koç University Hospital Assisted Reproduction Unit between October 2016 and August 2019 INTERVENTION(S): After ruling out endometrial pathology, blastocyst transfer was planned regardless of the EMT in the absence of increased serum progesterone level on the trigger day in fresh embryo transfer cycles or before commencing progesterone treatment in artificially prepared frozen-thawed ET cycles., Main Outcome Measure(s): The primary outcome was live birth. Live birth and miscarriage rates per ET were stratified according to fresh and frozen-thawed ET cycles for each millimeter of endometrial thickness. Receiver operator characteristic curve analyses were performed to evaluate the predictive value of EMT for live birth., Result(s): A total of 560 ET cycles, 273 fresh and 287 frozen-thawed, were included in the study. Relevant patient characteristics as well as EMTs were similar between women who achieved a live birth and those who did not after fresh or frozen-thawed ET. There was no linear association between EMT and live birth or miscarriage rates. Area under the curve values for EMT to predict live birth after fresh, frozen-thawed, and all ETs were 0.56, 0.47, and 0.52, respectively., Conclusion(s): Our results showed that the EMT was not predictive for live birth in either fresh or frozen-thawed ET cycles. Once intracavitary pathology and inadvertent progesterone exposure were excluded, women with thinner EMTs should not be denied their potential for live birth because it is comparable to that of those with thicker EMT., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The female genital tract is not exposed to seminal plasma during standard assisted reproductive technology (ART) cycles. However, it is thought that the inflammatory reaction triggered by seminal plasma may be beneficial by inducing maternal tolerance to paternal antigens expressed by the products of conception, and may increase the chance of successful implantation and live birth., Objectives: To assess the effectiveness and safety of application of seminal plasma to the female genital tract prior to embryo transfer in ART cycles., Search Methods: We searched the following databases from inception to October 2017: Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, CINAHL and PsycINFO. We also searched trial registers for ongoing trials, including International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Other sources searched were; Web of Knowledge, OpenGrey, LILACS, PubMed, Google Scholar and the reference lists of relevant articles., Selection Criteria: We included randomised controlled trials (RCTs) conducted among women undergoing ART, comparing any procedure that would expose the female genital tract to seminal plasma during the period starting five days before embryo transfer and ending two days after it versus no seminal plasma application., Data Collection and Analysis: Two review authors independently selected trials, assessed risk of bias, and extracted data. We pooled data to calculate relative risks (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I 2 statistic. We assessed the overall quality of the evidence for the main outcomes using GRADE methods. Our primary outcomes were live birth rate and miscarriage rate. Secondary outcomes were live birth/ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate and the incidence of other adverse events., Main Results: We included 11 RCTs (3215 women). The quality of the evidence ranged from very low to low. The main limitations were risk of bias (associated with poor reporting of allocation concealment and other methods) and imprecision for the primary outcome of live birth rate.Live birth rates: There was insufficient evidence to determine whether there was a difference between the groups with respect to live birth rates (RR 1.10, 95% CI 0.86 to 1.43; participants = 948; studies = 3; I 2 = 0%). Low quality evidence suggests that if the live birth rate following standard ART is 19% it will be between 16% and 27% with seminal plasma application.Miscarriage rate: There was insufficient evidence to determine whether there was a difference between the groups (RR 1.01, 95% CI 0.57 to 1.79; participants = 1209; studies = 4; I 2 = 0%). Low quality evidence suggests that if the miscarriage rate following standard ART is 3.7%, the miscarriage rate following seminal plasma application will be between 2.1% and 6.6%.Live birth or ongoing pregnancy rates: Seminal plasma application makes little or no difference in live birth or ongoing pregnancy rates (RR 1.19, 95% CI 0.95 to 1.49; participants = 1178; studies = 4; I 2 = 4%, low quality evidence). The evidence suggests that if the live birth or ongoing pregnancy rate following standard ART is 19.5% it will be between 18.5% and 29% with seminal plasma application.Clinical pregnancy rates: Seminal plasma application may increase clinical pregnancy rates (RR 1.15, 95% CI 1.01 to 1.31; participants = 2768; studies = 10; I 2 = 0%). Very low quality evidence suggests that if the clinical pregnancy rate following standard ART is 22.0% it will be between 22.2% and 28.8% with seminal plasma application. This finding should be regarded with caution, as a post-hoc sensitivity analysis restricted to studies at overall low risk of bias did not find a significant difference between the groups (RR 1.06, 95% CI 0.81 to 1.39; participants = 547; studies = 3; I 2 = 0%).Multiple pregnancy rate: Seminal plasma application may make little or no difference to multiple pregnancy rates (RR 1.11, 95% CI 0.76 to 1.64; participants = 1642; studies = 5; I 2 = 9%). Low quality evidence suggests that if the multiple pregnancy rate following standard ART is 7%, the multiple pregnancy rate following seminal plasma application will be between 5% and 11.4%.Ectopic pregnancy: There was insufficient evidence to determine whether seminal plasma application influences the risk of ectopic pregnancy (RR 1.59, 95% CI 0.20 to 12.78, participants =1521; studies = 5; I 2 = 0%) .Infectious complications or other adverse events: No data were available on these outcomes AUTHORS' CONCLUSIONS: In women undergoing ART, there was insufficient evidence to determine whether there was a difference between the seminal plasma and the standard ART group in rates of live birth (low-quality evidence) or miscarriage (low quality evidence). There was low quality evidence suggesting little or no difference between the groups in rates of live birth or ongoing pregnancy (composite outcome). We found low quality evidence that seminal plasma application may be associated with more clinical pregnancies than standard ART. There was low quality evidence suggesting little or no difference between the groups in rates of multiple pregnancy. There was insufficient evidence to reach any conclusions about the risk of ectopic pregnancy, and no data were available on infectious complications or other adverse events.We conclude that seminal plasma application is worth further investigation, focusing on live birth and miscarriage rates.

Objective: To compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening., Design: Randomized controlled trial., Setting: Private assisted reproduction center., Patient(s): A total of 179 patients undergoing IVF treatment using preimplantation genetic screening., Intervention(s): Patients were randomized at the time of hCG administration to either a freeze-all cycle or a fresh day 6 ET during the stimulated cycle., Main Outcome Measure(s): Implantation rates (sac/embryo transferred), ongoing pregnancy rates (PRs) (beyond 8 weeks), and live birth rate per ET in the primary transfer cycle., Result(s): Implantation rate per embryo transferred showed an improvement in the frozen group compared with the fresh group, but not significantly (75% vs. 67%). The ongoing PR (80% vs. 61%) and live birth rates (77% vs. 59%) were significantly higher in the frozen group compared with the fresh group., Conclusion(s): Either treatment protocol investigated in the present study can be a reasonable option for patients. Freezing all embryos allows for inclusion of all blastocysts in the cohort of embryos available for transfer, which also results in a higher proportion of patients reaching ET. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos., Clinical Trial Registration Number: NCT02000349., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze whether the use of a hyaluronan-enriched transfer medium (HETM) increases rates of implantation (IRs) and clinical pregnancy (CPRs), compared with the use of a conventional transfer medium after day 3 and day 5 embryo transfers., Design: Prospective randomized controlled trial., Setting: An assisted reproduction program in a private tertiary-care hospital in Turkey., Patient(s): A total of 1,282 consecutive fresh embryo transfer cycles (825 day 3 and 457 day 5) were randomly allocated into two groups. In 639 women, ET was effected with HETM, and in 643, it was effected with a conventional embryo transfer medium., Intervention(s): Embryo transfer using HETM or conventional embryo transfer medium., Main Outcome Measure(s): Clinical pregnancy rates and IRs were compared with regard to day of embryo transfer, women's age, quality of the transferred embryos, and presence of previous implantation failures., Result(s): Overall CPRs and IRs significantly increased with the use of HETM (CPR: 54.6% vs. 48.5%, odds ratio: 1.28, 95% confidence interval: 1.03-1.59; IR: 32% vs. 25%, odds ratio: 1.43, 95% confidence interval: 1.23-1.66, for HETM and control groups, respectively). The number needed to treat (NNT) for one additional pregnancy with routine use of HETM was 17. The beneficial effect was more prominent in women who were >35 years of age (NNT = 7), in women who had previous failed cycles (NNT = 7), and in women who had poor-quality embryos (NNT = 8)., Conclusion(s): The enrichment of transfer medium with hyaluronan increases CPRs and IRs, both for day 3 and day 5 embryo transfers. The beneficial effect was most evident in women who were >35 years of age, in women who had only poor-quality embryos available for transfer, and in women who had previous implantation failures.

Objective: To evaluate the effectiveness and safety of dual renin-angiotensin system (RAS) blockage together with total embryo cryopreservation for prevention of ovarian hyperstimulation syndrome (OHSS) in overstimulated patients undergoing IVF., Design: Retrospective case series., Setting: A private tertiary care hospital assisted reproduction program., Patient(s): Ten women at high risk for OHSS (mean E(2) level 9401 +/- 585 pg/mL on the day of hCG administration)., Intervention(s): Cancellation of ET and dual RAS blockage with an angiotensin receptor blocker (candesartan cilexetil) and an angiotensin-converting enzyme inhibitor (enalapril) starting from day 1 after oocyte retrieval. Embryos were cryopreserved and transferred in subsequent cycles., Main Outcome Measure(s): Development of OHSS and pregnancy and live birth rates after frozen-thawed ETs., Result(s): While eight women did not develop OHSS, two women (20%) developed severe OHSS requiring hospitalization. Subsequent frozen-thawed ETs resulted in an 80% clinical pregnancy rate and 40% live birth rate., Conclusion(s): Dual RAS blockage with total embryo cryopreservation is a relatively new strategy that was proposed for use in patients at high risk for OHSS. It should be stressed that complete elimination of the syndrome is not possible with this treatment. Subsequent pregnancy rates with the transfer of frozen-thawed embryos are high.

To investigate whether endometrial thickness (ET) independently affects the live birth rate (LBR) after embryo transfer. Retrospective study. Private assisted reproductive technology center. A total of 959 single euploid frozen embryo transfers. Vitrified euploid blastocyst transfer. Live birth rate per embryo transfer. The conditional density plots did not demonstrate either a linear relationship between the ET and LBR or a threshold below which the LBR decreased perceivably. Receiver operating characteristic curve analyses did not suggest a predictive value of the ET for the LBR. The area under the curve values were 0.55, 0.54, and 0.54 in the overall, programmed, and natural cycle transfers, respectively. Logistic regression analyses with age, embryo quality, day of trophectoderm biopsy, body mass index, and ET did not suggest an independent effect of the ET on the LBR. We did not identify a threshold of the ET that either precluded live birth or under which the LBR decreases perceivably. Common practice of cancelling embryo transfers when the ET is <7 mm may not be justified. Prospective studies, in which the management of the transfer cycle would not be altered by ET, would provide higher-quality evidence on the subject. [ABSTRACT FROM AUTHOR]

Background: The key to optimal timing of frozen embryo transfer (FET) is to synchronize the embryo with the receptive phase of the endometrium. Secretory transformation of the endometrium is induced by progesterone. In contrast, detection of the luteinizing hormone (LH) surge is the most common surrogate used to determine the start of secretory transformation and to schedule FET in a natural cycle. The accuracy of LH monitoring to schedule FET in a natural cycle relies heavily on the assumption that the period between the LH surge and ovulation is acceptably constant. This study will determine the period between LH rise and progesterone rise in ovulatory natural menstrual cycles. Methods: Retrospective observational study including 102 women who underwent ultrasound and endocrine monitoring for a frozen embryo transfer in a natural cycle. All women had serum LH, estradiol and progesterone levels measured on three consecutive days until (including) the day of ovulation defined with serum progesterone level exceeding 1ng/ml. Results: Twenty-one (20.6%) women had the LH rise 2 days prior to progesterone rise, 71 (69.6%) had on the day immediately preceding progesterone rise and 10 (9.8%) on the same day of progesterone rise. Women who had LH rise 2 days prior to progesterone rise had significantly higher body mass index and significantly lower serum AMH levels than women who had LH rise on the same day with progesterone rise. Conclusion: This study provides an unbiased account of the temporal relationship between LH and progesterone increase in a natural menstrual cycle. Variation in the period between LH rise and progesterone rise in ovulatory cycles likely has implications for the choice of marker for the start of secretory transformation in frozen embryo transfer cycles. The study participants are representative of the relevant population of women undergoing frozen embryo transfer in a natural cycle. [ABSTRACT FROM AUTHOR]

PGDIS Position statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst statement. Sir, [2] report live births from blastocysts with "abnormal" results, which were previously denied transfer. In the study by [2], after excluding results predicting "mosaicism" and "segmental aberrations", the transfer embryos with uniform whole chromosome aneuploidies, led to a clinical pregnancy loss rate of 100% (5/5 transfers with exclusively full chromosome aneuploid embryos). [Extracted from the article]

Progestins are capable of suppressing endogenous luteinizing hormone (LH) secretion from the pituitary; are less expensive than GnRH analogues. This systematic review summarizes the effectiveness of progestins as compared with GnRH analogues and identifies some of the future research perspectives. Several public resources were screened with a combination of keywords related to assisted reproductive technology, progesterone, GnRH analogue and ovarian stimulation. Overall, duration of stimulation, gonadotropin consumption and oocyte yield were similar with progestins and GnRH analogues. The live birth, ongoing and clinical pregnancy rates per embryo transfer were similar with progestins and GnRH analogues. There is still a low quality of evidence. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. As a wider implication, progestins can present an effective option for women who do not contemplate a fresh embryo transfer, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles. [ABSTRACT FROM AUTHOR]

To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment. International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management. A systematic review without meta-analysis of studies published in English from January 2015 to May 2022. Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon—occurring in <5% of couples with infertility—and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence. True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age). Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement. [ABSTRACT FROM AUTHOR]

We performed a literature review of studies comparing the effectiveness of progestins in preventing premature ovulation during ovarian stimulation for assisted reproductive technology (ART). Five randomized trials and cohort studies involving a total of 2404 women, which compared; i) two different progestins or ii) two different doses of the same progestin were included. The primary outcome was live birth rate (LBR) per woman. Secondary outcomes were live birth or ongoing pregnancy (LB/OP) per woman and per embryo transfer (ET), ongoing pregnancy, clinical pregnancy, positive pregnancy test, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotropin consumption. The primary outcome was not reported in most studies however there were no differences between progestins for secondary outcomes. All progestins seem to effectively prevent premature ovulation in ART cycles. Low-quality evidence suggests that progestins can effectively prevent premature ovulation in ART cycles. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical outcome of single-embryo transfer (SET) with double-embryo transfer (DET) in in vitro maturation (IVM) cycles performed in patients with polycystic ovary syndrome (PCOS), and to determine which factors predict those outcomes.Design: A retrospective analysis.Setting: Private assisted reproduction center.Patient(s): One hundred and fifty-nine women with PCOS.Intervention(s): In vitro maturation with elective SET or DET conducted between September 2007 and May 2014.Main Outcome Measure(s): Live-birth rates.Result(s): Single-embryo transfer was performed in 83 patients (52.2%), and DET was performed in 76 patients (47.7%). When compared with the patients who had DET, the patients who had SET were statistically significantly younger (32.4 ± 3.5 vs. 24.1 ± 4.2 years) and had a shorter infertility duration (9.2 ± 4.5 vs. 4.4 ± 2.1 years), fewer previous ART cycles (<2 prior attempts, 39.5% vs. 6%; ≥2 prior attempts, 60.5% vs. 0), fewer collected oocytes (15.1 ± 4.6 vs. 12.6 ± 3.8), fewer metaphase II oocytes (9.0 ± 4.1 vs. 5.7 ± 2.9), fewer fertilized oocytes (8.2 ± 3.7 vs. 3.6 ± 2.3), and a higher implantation rate (27% vs. 47%). The SET and DET groups had similar embryo quality and similar clinical pregnancy (44.6% vs. 44.7%) and live-birth rates (34.9% vs. 34.2%). Twin pregnancy rates were statistically significantly higher in the DET compared with the SET groups (9.2% vs. 2.4%).Conclusion(s): In vitro maturation is a successful assisted reproduction technique that can be an alternative to conventional in vitro fertilization in women presenting with PCOS-related infertility. Our observations suggest that SET is a feasible option to prevent multiple pregnancies while maintaining the live-birth rate. [ABSTRACT FROM AUTHOR]