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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: In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain.Objective and Rationale: This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals.Search Methods: PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible.Outcomes: From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients.Wider Implications: This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil. [ABSTRACT FROM AUTHOR]

Study Question: What is the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the outcome of a pregnancy after medically assisted reproduction (MAR)?Summary Answer: Our results suggest that MAR pregnancies are not differentially affected by SARS-CoV-2 infection compared to spontaneous pregnancies.What Is Known Already: Information on the effects of coronavirus disease 2019 (COVID-19) on pregnancy after MAR is scarce when women get infected during MAR or early pregnancy, even though such information is vital for informing women seeking pregnancy.Study Design, Size, Duration: Data from SARS-CoV-2 affected MAR pregnancies were collected between May 2020 and June 2021 through a voluntary data collection, organised by the European Society of Human Reproduction and Embryology (ESHRE).Participants/materials, Setting, Methods: All ESHRE members were invited to participate to an online data collection for SARS-CoV-2-infected MAR pregnancies.Main Results and the Role Of Chance: The dataset includes 80 cases from 32 countries, including 67 live births, 10 miscarriages, 2 stillbirths and 1 maternal death. An additional 25pregnancies were ongoing at the time of writing.Limitations, Reasons For Caution: An international data registry based on voluntary contribution can be subject to selective reporting with possible risks of over- or under-estimation.Wider Implications Of the Findings: The current data can be used to guide clinical decisions in the care of women pregnant after MAR, in the context of the COVID-19 pandemic.Study Funding/competing Interest(s): The authors acknowledge the support of ESHRE for the data registry and meetings. J.S.T. reports grants or contracts from Sigrid Juselius Foundation, EU and Helsinki University Hospital Funds, outside the scope of the current work. The other authors declare that they have no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

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]

The coronavirus disease 2019 (COVID-19) pandemic created a significant impact on medically assisted reproduction (MAR) services. ESHRE decided to mobilize resources in order to collect, analyse, monitor, prepare and disseminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) knowledge specifically related to ART and early pregnancy. This article presents the impact of the SARS-CoV-2 pandemic focusing on reproductive healthcare. It details the rationale behind the guidance prepared to support MAR services in organizing and managing the re-start of treatments or in case of any future wave of COVID-19 disease. The guidance includes information on patient selection and informed consent, staff and patient triage and testing, adaptation of ART services, treatment planning and code of conduct. The initiatives detailed in this article are not necessarily COVID-specific and such action plans could be applied effectively to manage similar emergency situations in different areas of medicine, in the future. [ABSTRACT FROM AUTHOR]

STUDY QUESTION How did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? SUMMARY ANSWER MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. WHAT IS KNOWN ALREADY With the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. STUDY DESIGN, SIZE, DURATION A structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. PARTICIPANTS/MATERIALS, SETTING, METHODS The information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. MAIN RESULTS AND THE ROLE OF CHANCE By aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. WIDER IMPLICATIONS OF THE FINDINGS The current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations. STUDY FUNDING/COMPETING INTEREST(S) There was no funding for the study, apart from technical support from ESHRE. The authors had no COI to disclose. [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]

Study Question: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma?Summary Answer: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma.What Is Already Known: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas.Study Design, Size, Duration: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period.Participants/materials, Setting, Methods: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded.Main Results and the Role Of Chance: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3).Limitations, Reasons For Caution: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment.Wider Implications Of the Findings: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified.Study Funding/competing Interest(s): No funding or competing interests to declare.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to provide an overview of the studies investigating a possible association between thrombophilia and assisted reproductive technology (ART) outcome. Methods: This is a literature review. Results: Congenital thrombophilias (CoT) are reported to be associated with pregnancy loss. However, the association between CoT and early pregnancy loss is weak and does not necessarily support causation. CoT are more likely to be associated with late fetal loss. Even though data pooled from case-control and cohort studies suggest an increased risk of ART failure in women with CoTs, there seems no association when the analysis is confined to better quality cohort studies. The evidence supporting anticoagulation to improve ART outcome in CoT carriers is weak. Likewise, studies on antiphospholipid antibodies (APAs) and ART outcome suffer from multiple methodological limitations and a detrimental impact of APA positivity is controversial. Empirical administration of heparin or low molecular weight heparin to women with recurrent ART failures is supported by weak evidence. Importantly, thrombophilias are likely to increase thrombotic complications after ovarian stimulation for ART. Conclusions: Current evidence does not support routinely testing for or treatment of thrombophilia in the setting of ART nor in couples with implantation failure. A careful personal and family history should be obtained and a risk assessment for thrombotic complications should be made in every woman undergoing ovarian stimulation. If positive, testing for thrombophilia is warranted. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to determine whether high E2 levels after controlled ovarian hyperstimulation affect TSH. Methods: Patients completing ART cycles between April-October 2010 were eligible for this cohort study. 180 patients were recruited however those with known thyroid disease were excluded. The final analysis included 154 subjects. Blood was collected at each visit during the ART cycle as well as at the pregnancy test. Samples were frozen at −20 °C and analyzed together for E2 and TSH using the same assay kit once all patients had completed their cycles. All participants were treated at the McGill University Health Center. A paired t-test was used to study the difference in TSH levels recorded at maximal and minimal Estradiol levels during ovarian stimulation. Multiple regression analysis was then used to determine if factors such as anti-thyroid antibodies and ovarian reserve measures affect this change in TSH. We used multiple imputation methods to account for missing data. Results: As E2 levels rose from low to supra-physiologic levels during treatment, TSH levels also rose significantly. This increase was clinically significant by the time of pregnancy test. The factors that potentially affected the change in TSH were: male factor/tubal factor infertility, type of protocol used as well as the presence of thyroid antibodies. Conclusions: Although TSH increases during ART, this change only becomes clinically significant on the day of pregnancy test. Future studies should examine TSH changes specifically in certain “at-risk” sub-groups such as those with antibodies and known thyroid disease. [ABSTRACT FROM AUTHOR]

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 E2 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. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE," by A. Andersen Nyboe and colleagues, published in a 2009 issue of the journal.

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]

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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a flexible progestin primed ovarian stimulation (fPPOS) protocol is effective for preventing premature ovulation.Design: Retrospective cohort study.Setting: Private assisted reproduction center.Patient(s): Eighty-seven oocyte donors and 191 recipients of fresh oocytes.Intervention(s): Each donor was stimulated with a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in one cycle and with the new fPPOS protocol in the other, within a period of 6 months. FSH was started on cycle day 2-3, and 0.25 mg/day GnRH antagonist or 10 mg/day medroxyprogesterone acetate (MPA) was started on stimulation day 7 or when the leading follicle reached 14 mm, whichever came first.Main Outcome Measure(s): Duration of stimulation, gonadotropin consumption, duration of GnRH antagonist or MPA administration, number of metaphase II oocytes, and pregnancy rates in fresh oocyte recipients.Results: Duration of stimulation was 11 (10-11) days in both groups. Total gonadotropin consumption was similar. Pituitary suppression was started on day 7 and lasted for 5 days in each group. There were no premature ovulations in any group. The fPPOS yielded a significantly higher number of cumulus oocyte complexes than GnRH antagonist cycles (33 [21-39] vs. 26 [18-36], respectively). Likewise, the fPPOS generated significantly more metaphase II oocytes than GnRH antagonist cycles (24 [17-34] vs. 21 [15-28], respectively). Recipients of fresh oocytes from fPPOS and GnRH antagonist cycles had similar cleavage, blastulation, implantation, and live birth/ongoing pregnancy rates (50% vs. 48.6%).Conclusion(s): FPPOS with MPA seems to be an effective choice for preventing premature ovulation in women undergoing ovarian stimulation without compromising oocyte quality. [ABSTRACT FROM AUTHOR]