Early GnRH-agonist therapy does not negatively impact the endometrial repair process or live birth rate.

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

In vitro fertilization outcome based on the detailed early luteal phase trajectory of hormones: a prospective cohort study.

BACKGROUND: Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer. METHODS: This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18-38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile. RESULTS: Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28-3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03-4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth. CONCLUSIONS: These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF. TRIAL REGISTRATION: NCT04693624 ( www. CLINICALTRIALS: gov ).

Births: Final Data for 2022.

Objectives- This report presents 2022 data on U.S. births by selected characteristics. Trends in fertility patterns and maternal and infant characteristics are described. Methods-Descriptive tabulations based on birth certificates of the 3.67 million births registered in 2022 are shown by maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates also are shown. Trends for 2010 to 2022 are presented for selected items, and by race and Hispanic origin for 2016-2022. Results-A total of 3,667,758 births occurred in the United States in 2022, essentially unchanged from 2021. The general fertility rate declined 1% from 2021 to 56.0 births per 1,000 females ages 15-44 in 2022. The birth rate for females ages 15-19 declined 2% from 2021 to 2022; birth rates fell 7% for women ages 20-24, rose 1% to 5% for women ages 25-29 and 35-44, and rose 12% for women ages 45-49 (the first increase since 2016). The total fertility rate declined less than 1% to 1,656.5 births per 1,000 women in 2022. Birth rates declined for unmarried women but increased for married women from 2021 to 2022. Prenatal care beginning in the first trimester declined to 77.0% in 2022; the percentage of women who smoked during pregnancy declined to 3.7%. The cesarean delivery rate was unchanged in 2022 (32.1%); Medicaid was the source of payment for 41.3% of births. The preterm birth rate declined 1% to 10.38%; the low birthweight rate rose 1% to 8.60%. The twin birth rate was unchanged in 2022 (31.2 per 1,000 births); the 2% decrease in the triplet and higher-order multiple birth rate.

[Live birth rates after breast cancer among women who desired a child]. / Naissances vivantes après cancer du sein parmi les femmes désirant un enfant.

INTRODUCTION: In France, the breast cancer is the most common cancer among women under the age of 40. From 38 to 70% of women have not fulfilled their parental plans at the time of diagnosis. The gonadotoxicity of the treatments and the follicular physiological decline linked to age can become an obstacle to this project. METHODS: Among the patients, 386 were treated for breast cancer at the Centre Georges-François-Leclerc in Dijon between January 2011 and December 2018 were identified. 192 patients aged under 39 met the inclusion criteria. We excluded metastatic cancers, cancer in situ and pregnant patients at diagnosis. A total of 124 patients agreed to participate in the study. The included patients filled out a self-questionnaire. Data were collected from the patient's electronic medical. The primary endpoint of this study was the live birth rate. RESULT: Among women who desired a child after breast cancer, the overall rate of live births was 36.2 % (21/58). Most achieved pregnancies were spontaneous (90.5 %). No factor was significantly associated with the absence of obtaining birth. Fertility was preserved by oocyte cryopreservation in 13.8 % of patients (17/124). The median time to conception in patients who received chemotherapy was 8 months [1.0-60.0] vs 2 months [1.0-7.0] in women who did not receive chemotherapy. DISCUSSION: The non-negligible proportion of live births following spontaneous pregnancy after breast cancer allows us to be reassuring for patients. However, the emergence of new chemotherapy protocols whose consequences on long-term gonadotoxicity are still not well known requires further studies and prompts the promotion of fertility preservation as a precautionary measure.

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients.

STUDY QUESTION: What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER: The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5-99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY: The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION: An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93-1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58-1.21, P = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5-99.6%). LIMITATIONS, REASONS FOR CAUTION: Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS: Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Meta-analysis of trigger timing in normal responders undergoing GnRH antagonist ovarian hyperstimulation protocol.

IMPORTANCE: The first meta-analysis focused only on gonadotropin-releasing hormone (GnRH) antagonists, which helped determine the effect of delay trigger on pregnancy outcomes. OBJECTIVE: To evaluate the impact of delay trigger compared with standard trigger in normal responders undergoing GnRH antagonist protocol in improving pregnancy outcomes. METHODS: Studies published before April 2023 in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM databases were searched. Randomized controlled trials (RCTs) and cohort studies conducted in normal responders reporting the efficacy of delay trigger using GnRH antagonist protocol were included. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for categorical variables with their corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q test. RESULTS: Endpoints, including clinical pregnancy rate (CPR), live birth rate (LBR), the number of oocyte retrievals and embryos, and fertilization rate, were analyzed. Six (6) clinical studies (4 RCTs and 2 cohort studies) with 1,360 subjects were included. The pooled results showed that the number of oocyte retrievals (MD: 1.20, 95% CI: 1.10, 1.30, p < 0.01), fertilization rate (MD: 0.64, 95% CI: 0.29, 0.99, p < 0.01) and days of stimulation (MD: 0.95; 95% CI: 0.54, 1.37; p < 0.01) in the delay trigger group was significantly higher than that in the standard trigger group. However, there was no significant difference in the number of embryos (MD: 0.19, 95% CI: -0.29, 0.67, p = 0.44), CPR (OR: 1.12; 95% CI: 0.72, 1.75; p = 0.062), and LBR (OR: 1.23; 95% CI: 0.90, 1.66; p = 0.19) between the two trigger groups. CONCLUSION: Delaying trigger time in GnRH antagonist protocol increased the number of oocytes retrieved but not the number of embryos. Furthermore, delay trigger shot was not associated with a clinical benefit towards CPR and LBR in women who underwent fresh embryo transfer cycles. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO), registration number: CRD42023413217.

Childbirth rates in women with myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15-44 years with an MPN diagnosis 1973-2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68-0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86-1.22) while the HR was 0.50 (0.33-0.76) in PV and 0.45 (0.28-0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Does surgery for colorectal endometriosis prior to IVF±ICSI have an impact on cumulative live birth rates?

RESEARCH QUESTION: Does colorectal endometriosis surgery prior to IVF ± intracytoplasmic sperm injection (ICSI) impact cumulative live birth rates? DESIGN: This retrospective, monocentric study (Lille University Hospital) was conducted between 1 January 2007 and 31 December 2018. Two groups of patients from the JFIV database were included: a group undergoing IVF±ICSI alone (120 patients, 215 oocyte retrievals), and a group undergoing surgery and then IVF±ICSI (69 patients, 109 oocyte retrievals). The mode of management was decided after a multidisciplinary team meeting. Different criteria such as age (cut-off 35 years), anti-Müllerian hormone concentration (cut off 2 ng/ml), imaging results and the patient's symptomatology were considered: the most symptomatic patients underwent surgery prior to IVF±ICSI. The cumulative clinical pregnancy and live birth rates obtained after four IVF attempts were estimated and compared between the two groups using competing risk survival methods. RESULTS: The cumulative live birth rates after four IVF attempts in the two groups were not statistically significantly different (50.8% in the IVF±ICSI group versus 52.2% in the surgery followed by IVF±ICSI group, P = 0.43). The results for the cumulative clinical pregnancy rates were the same (56.7% in the IVF±ICSI group versus 58% in the surgery followed by IVF±ICSI group, P = 0.47). CONCLUSION: The study shows that cumulative live birth and pregnancy rates were similar in infertile patients with colorectal endometriosis who underwent IVF±ICSI either with or without prior colorectal endometriosis surgery.

ESHRE guideline: number of embryos to transfer during IVF/ICSI†.

STUDY QUESTION: Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)? SUMMARY ANSWER: No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI. WHAT IS KNOWN ALREADY: DET is correlated with a higher rate of multiple pregnancy, leading to a subsequent increase in complications for both mother and babies. These complications include preterm birth, low birthweight, and other perinatal adverse outcomes. To mitigate the risks associated with multiple pregnancy, eSET is recommended by international and national professional organizations as the preferred approach in ART. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development and update of ESHRE guidelines. Literature searches were performed in PUBMED/MEDLINE and Cochrane databases, and relevant papers published up to May 2023, written in English, were included. Live birth rate, cumulative live birth rate, and multiple pregnancy rate were considered as critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were discussed until a consensus was reached within the Guideline Development Group (GDG). A stakeholder review was organized after the guideline draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 35 recommendations on the medical and non-medical risks associated with multiple pregnancies and on the clinical and embryological factors to be considered when deciding on the number of embryos to transfer. These recommendations include 25 evidence-based recommendations, of which 24 were formulated as strong recommendations and one as conditional, and 10 good practice points. Of the evidence-based recommendations, seven (28%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (three recommendations; 12%), or very low-quality evidence (15 recommendations; 60%). Owing to the lack of evidence-based research, the guideline also clearly mentions recommendations for future studies. LIMITATIONS, REASONS FOR CAUTION: The guideline assessed different factors one by one based on existing evidence. However, in real life, clinicians' decisions are based on several prognostic factors related to each patient's case. Furthermore, the evidence from randomized controlled trials is too scarce to formulate high-quality evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides health professionals with clear advice on best practice in the decision-making process during IVF/ICSI, based on the best evidence currently available, and recommendations on relevant information that should be communicated to patients. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTEREST(S): The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, the literature searches, and the dissemination of the guideline. The guideline group members did not receive payment. DPB declared receiving honoraria for lectures from Merck, Ferring, and Gedeon Richter. She is a member of ESHRE EXCO, and the Mediterranean Society for reproductive medicine and the president of the Croatian Society for Gynaecological Endocrinology and Reproductive Medicine. CDG is the past Chair of the ESHRE EIM Consortium and a paid deputy member of the Editorial board of Human Reproduction. IR declared receiving reimbursement from ESHRE and EDCD for attending meetings. She holds an unpaid leadership role in OBBCSSR, ECDC Sohonet, and AER. KAR-W declared receiving grants for clinical researchers and funding provision to the institution from the Swedish Cancer Society (200170F), the Senior Clinical Investigator Award, Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council FoU (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963), NovoNordisk, Merck and Ferring Pharmaceuticals. She received consulting fees from the Swedish Ministry of Health and Welfare. She received honoraria from Roche, Pfizer, and Organon for chairmanship and lectures. She received support from Organon for attending meetings. She participated in advisory boards for Merck, Nordic countries, and Ferring. She declared receiving time-lapse equipment and grants with payment to institution for pre-clinical research from Merck pharmaceuticals and from Ferring. SS-R received research funding from Roche Diagnostics, Organon/MSD, Theramex, and Gedeo-Richter. He received consulting fees from Organon/MSD, Ferring Pharmaceuticals, and Merck Serono. He declared receiving honoraria for lectures from Ferring Pharmaceuticals, Besins, Organon/MSD, Theramex, and Gedeon Richter. He received support for attending Gedeon Richter meetings and participated in the Data Safety Monitoring Board of the T-TRANSPORT trial. He is the Deputy of ESHRE SQART special interest group. He holds stock options in IVI Lisboa and received equipment and other services from Roche Diagnostics and Ferring Pharmaceuticals. KT declared receiving payment for honoraria for giving lectures from Merck Serono and Organon. She is member of the safety advisory board of EDQM. She holds a leadership role in the ICCBBA board of directors. ZV received reimbursement from ESHRE for attending meetings. She also received research grants from ESHRE and Juhani Aaltonen Foundation. She is the coordinator of EHSRE SQART special interest group. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (full disclaimer available at https://www.eshre.eu/Guidelines-and-Legal).

Association between proliferative-to-secretory endometrial compaction and pregnancy outcomes after embryo transfer: a systematic review and meta-analysis.

STUDY QUESTION: Does the change in endometrial thickness (EMT) from the end of the follicular/estrogen phase to the day of embryo transfer (ET) determine subsequent pregnancy outcomes? SUMMARY ANSWER: Endometrial compaction from the late-proliferative to secretory phase is not associated with live birth rate (LBR) and other pregnancy outcomes. WHAT IS KNOWN ALREADY: Endometrial compaction has been suggested to be indicative of endometrial responsiveness to progesterone, and its association with ET outcome has been investigated but is controversial. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was carried out. PubMed, EMBASE, and Web of Science were searched to identify relevant studies from inception to 18 November 2022. The reference lists of included studies were also manually screened for any additional publications. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort studies comparing ET pregnancy outcomes between patients with and without endometrial compaction were included. A review of the studies for inclusion, data extraction, and quality assessment was performed by two independent reviewers. The effect size was synthesized as odds ratio (OR) with 95% CI using a random-effects model. Heterogeneity and publication bias were assessed by the I2 statistic and Egger's test, respectively. The primary outcome was LBR. Secondary outcomes included biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate (MR), ongoing pregnancy rate (OPR), and ectopic pregnancy rate (EPR). MAIN RESULTS AND THE ROLE OF CHANCE: Seventeen cohort studies involving 18 973 ET cycles fulfilled the eligibility criteria. The pooled results revealed that there were no significant differences between endometrial compaction and non-compaction groups in LBR (crude OR (cOR) = 0.95, 95% CI 0.87-1.04; I2 = 0%; adjusted OR (aOR) = 1.02, 95% CI 0.87-1.19, I2 = 79%), BPR (cOR = 0.93, 95% CI 0.81-1.06; I2 = 0%; aOR = 0.88, 95% CI 0.75-1.03, I2 = 0%), CPR (cOR = 0.98, 95% CI 0.81-1.18; I2 = 70%; aOR = 0.86, 95% CI 0.72-1.02, I2 = 13%), MR (cOR = 1.09, 95% CI 0.90-1.32; I2 = 0%; aOR = 0.91, 95% CI 0.64-1.31; I2 = 0%), and EPR (cOR = 0.70, 95% CI 0.31-1.61; I2 = 61%). The OPR was marginally higher in crude analysis (cOR = 1.48, 95% CI 1.01-2.16; I2 = 81%) among women with compacted endometrium, but was not evident in adjusted results (aOR = 1.36, 95% CI 0.86-2.14; I2 = 84%). Consistently, the pooled estimate of LBR remained comparable in further subgroup and sensitivity analyses according to the degree of compaction (0%, 5%, 10%, 15%, or 20%), type of ET (fresh, frozen, or euploid only), and endometrial preparation protocol (natural or artificial). No publication bias was observed based on Egger's test. LIMITATIONS, REASONS FOR CAUTION: Although the number of included studies is sufficient, data on certain measures, such as EPR, are limited. The inherent bias and residual confounding were also inevitable owing to the observational study design. Furthermore, inconsistent definitions of pregnancy outcomes may affect the accuracy of our pooled analysis. WIDER IMPLICATIONS OF THE FINDINGS: Given the lack of prognostic value, assessing endometrial compaction or repeated EMT measurement on the day of ET may not be necessary or warranted. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Natural Science Foundation of Jiangxi Province (20224BAB216025), National Natural Science Foundation of China (82260315), and Central Funds Guiding the Local Science and Technology Development (20221ZDG020071). The authors have no conflicts of interest to declare. REGISTRATION NUMBER: CRD42022384539 (PROSPERO).

Cumulative live birth rate of in vitro fertilization cycle via progestin-primed ovarian stimulation versus gonadotropin-releasing hormone antagonist protocol in infertile women with normal ovarian reserve: an open-label, randomized controlled trial.

This study aimed to evaluate the cumulative live birth rate (cLBR) of progestin-primed ovarian stimulation (PPOS) protocol versus gonadotropin-releasing hormone antagonist (GnRH-ant) protocol for in vitro fertilization (IVF) cycle in infertile women with normal ovarian reserve (NOR). Infertile women with NOR who underwent their first IVF cycle were enrolled in an open-label randomized controlled trial. Patients were randomly assigned 1:1 to receive a freeze-all strategy with delayed embryo transfer (PPOS group, n = 174) and fresh embryo transfer first (GnRH-ant group, n = 174). The primary outcome was the cLBR per aspiration. The cLBR between the PPOS group and GnRH-ant group were comparable (55.75% vs. 52.87%, p = 0.591). A premature luteinizing hormone surge was not observed in the PPOS group, while there were six cases (3.45%) in the GnRH-ant group, but no premature ovulation in either of the groups. The pregnancy outcomes, including implantation rate, clinical pregnancy rate and miscarriage rate, were all comparable. In addition, the number of retrieved oocytes, mature oocytes and viable embryos were similar (all p > 0.05) between the two groups.

Nonlinear relationship between gonadotropin total dose applied and live birth rates in non-PCOS patients: a retrospective cohort study.

The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction < 0.05).

The "freeze-all" strategy seems to improve the chances of birth in adenomyosis-affected women.

OBJECTIVE: To compare assisted reproductive technologies (ARTs) outcomes between fresh vs. freeze-all strategies in infertile women affected by adenomyosis. DESIGN: A single-center observational study. SETTINGS: University hospital-based research center. PATIENTS: Adenomyosis-affected women undergoing blastocyst embryo transfer after in vitro fertilization and intracytoplasmic sperm injection between January 1, 2018, and November 31, 2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). INTERVENTION(S): Women who underwent a freeze-all strategy were compared with those who underwent a fresh embryo transfer (ET) strategy. MAIN OUTCOME MEASURE(S): Cumulative live birth rate (LBR). RESULTS: A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR (86 [44.1%] vs. 34 [30.6%], respectively), and the cumulative ongoing pregnancy rate (88 [45.1%] vs. 36 [32.4%], respectively) were significantly higher in the freeze-all group compared with the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared with fresh ET (odds ratio = 1.80; 95% confidence interval = 1.02-3.16). CONCLUSION: The freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative LBRs. Our preliminary results suggest that the freeze-all strategy is an attractive option that increases ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Comparison of Letrozole and Clomiphene Citrate in Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To comprehensively summarize the evidence, a systematic review and meta-analysis of randomized clinical trials (RCTs) was carried out to assess the effect of letrozole and CC on pregnancy outcomes in PCOS patients. We searched PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2023. We included RCTs conducted on PCOS women comparing letrozole to CC and assessing endometrial thickness, the number and size of follicles, and ovulation and pregnancy rates. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) using the random-effects model. Heterogeneity was examined using the I2 statistic. Fifty trials met our inclusion criteria. The mean endometrial thickness was significantly higher in the letrozole group compared to CC group (SMD: 0.89; 95% CI: 0.49, 1.28; I2=97.72%); however, the number of follicles was higher in the CC group (SMD: -0.56; 95% CI: -0.96, -0.17; I2=96.34%). Furthermore, letrozole intake induced higher ovulation rate (RR: 1.20; 95% CI: 1.13, 1.26; I2=54.49%) and pregnancy rate (RR: 1.44; 95% CI: 1.28, 1.62; I2=65.58%) compared to CC. Compared to CC, letrozole has a positive effect on endometrial thickness, monofollicular development, and ovulation and pregnancy rates suggesting that letrozole may be a strong alternative to CC as a first-line medical intervention for chronic anovulation in PCOS women. Larger studies are warranted to further clarify these findings.

Live birth rates in in vitro fertilization cycles with five or fewer follicles.

PURPOSE: To evaluate live birth rates (LBRs) for in vitro fertilization (IVF) cycles with ≤5 follicles at trigger, with the goal of helping patients with low follicle counts decide whether to proceed to retrieval. METHODS: This is a retrospective cohort study from an urban, university-affiliated fertility center. All IVF cycles that yielded <10 oocytes between 2016 and 2020 were reviewed. Cycles were included if <5 follicles measuring >14 mm were verified on trigger day. The primary outcome was LBR per retrieval after fresh or frozen transfer. Secondary outcomes were number of oocytes, mature oocytes, 2-pronuclear zygotes (2-PNs), blastocysts for transfer/biopsy, and euploid blastocysts (if preimplantation genetic testing for aneuploidy (PGT-A) was used). RESULTS: 1502 cycles (900 with PGT-A) from 972 patients were included. Mean number of oocytes, mature oocytes, 2-PNs, blastocysts for transfer/biopsy, and euploid blastocysts differed by follicle number (p < 0.001). Across all age groups, there were differences in LBR associated with follicle number (p < 0.001). However, within age groups, not all results were significant. For example, for patients <35 years, LBR did not differ by follicle number and among patients 35-37 years; LBR with two or three follicles was lower than with five (p < 0.02). LBR for patients 35-40 years was <20% with 1-3 follicles and 25-40% with 4-5 follicles. LBR for patients >41 years was <5% with 1-3 follicles and <15% with 4-5 follicles. CONCLUSION: As expected, LBR is higher with more follicles. Providing patients with <5 follicles with specific data can help them weigh the emotional, physical, and financial costs of retrieval.

Live birth rate of gonadotropin-releasing hormone antagonist versus luteal phase gonadotropin-releasing hormone agonist protocol in IVF/ICSI: a systematic review and meta-analysis.

In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.

hMG addition affects the change in progesterone level during IVF stimulation and LBR: a retrospective cohort study.

BACKGROUND: Premature progesterone (P) rise during IVF stimulation reduces endometrial receptivity and is associated with lower pregnancy rates following embryo transfer (ET), which can influence provider recommendation for fresh or frozen ET. This study aimed to determine whether change in P level between in IVF baseline and trigger (𝚫P) is predictive of pregnancy outcome following fresh ET, and whether the ratio of gonadotropins influences P rise and, as a result, clinical pregnancy outcomes: clinical pregnancy rate (CPR) and live birth rates (LBR). METHODS: Retrospective cohort study at a single fertility center at an academic institution. The peak P level and 𝚫P were modeled in relation to prediction of CPR and LBR, and the ratios of hMG:rFSH were also modeled in relation to prediction of peak P level on day of trigger, 𝚫P, and CPR/LBR in a total of 291 patients undergoing fresh embryo transfer after controlled ovarian hyperstimulation-IVF (COH-IVF). RESULTS: 𝚫P correlates with CPR, with the most predictive range for success as 𝚫P 0.7-0.85 ng/mL (p = 0.005, 95% CI 0.635, 3.636; predicting CPR of 88.9%). The optimal range for peak P in regard to pregnancy outcome was 0.15-1.349 ng/mL (p = 0.01; 95% CI for coefficient in model 0.48-3.570). A multivariable logistic model for prediction of CPR and LBR using either peak or 𝚫P supported a stronger association between 𝚫P and CPR/LBR as compared to peak P. Furthermore, an hMG:rFSH ratio of > 0.6 was predictive of lowest peak P (p = 0.010, 95% CI 0.035, 0.256) and smallest 𝚫P (p = 0.012, 95% CI 0.030, 0.243) during COH-IVF cycles. Highest CPRs were observed within hMG:rFSH ratios of 0.3-0.4 [75.6% vs. 62.5% within and outside of the range, respectively, (p = 0.023, 95% CI 0.119, 1.618)]. Highest LBRs were seen within the range of 0.3-0.6 hMG:rFSH, [LBR of 55.4% vs. 41.4% (p = 0.010, 95% CI 0.176, 1.311)]. CONCLUSIONS: Our data supports use of 𝚫P to best predict pregnancy rates and therefore can improve clinical decision making as to when fresh ET is most appropriate. Furthermore, we found optimal gonadotropin ratios can be considered to minimize P rise and to optimize CPR/LBR, emphasizing the importance of luteinizing hormone (LH) activity in COH-IVF cycles.

Which transfer day results in the highest live birth rate for PCOS patients undergoing in vitro fertilization?

BACKGROUND: Polycystic ovary syndrome (PCOS) has unusual levels of hormones. The hormone receptors in the endometrium have a hostile effect and make the microenvironment unfavorable for embryo implantation. The use of gonadotropin stimulation during in vitro fertilization (IVF) may have an impact on embryo implantation and live birth rate. According to recent data, the clinical results of day 4 embryo transfer (D4 transfer) were on par with those of day 5 embryo transfer (D5 transfer) in IVF-ET. There are few studies comparing the outcomes of transplants with various etiologies and days. The purpose of this study was to determine which transfer day had the best result for PCOS patients undergoing IVF. METHODS: This retrospective cohort study was conducted in the Xingtai Infertility Specialist Hospital between January 2017 and November 2021. A total of 1,664 fresh ART cycles met inclusion criteria, including 242 PCOS transfers and 1422 tubal factor infertility transfers. CONCLUSIONS: PCOS individuals had the highest live birth rate on D4 transferred. It was not need to culture embryos to blastocysts to optimize embryo transfer for PCOS women. This could be a novel approach to transplantation for PCOS.

The association between serum prolactin levels and live birth rates in non-PCOS patients: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: This paper aimed to analyze the relationship between baseline prolactin (PRL) levels and live birth rates (LBRs) in patients undergoing embryo transfer who did not have polycystic ovarian syndrome (PCOS) using a retrospective design. Patient(s): A total of 20,877 patients who had undergone IVF/intracytoplasmic sperm injection (ICSI) between December 2014 and December 2019. MATERIALS AND METHODS: We examined the association between PRL concentrations and LBRs using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was developed. RESULTS: Following adjustment for confounding factors, multivariate regression analysis confirmed a statistically significant correlation between serum PRL and LBR. Particularly, when blood PRL content was less than 14.8 ng/mL, there exists a positive relation between serum PRL and LBRs. In contrast, once PRL concentrations surpassed the inflection point at 14.8 ng/mL, a meaningful relationship could no longer be inferred between serum PRL and LBR. CONCLUSIONS: Basal serum PRL levels were segmentally connected with LBRs.