Primary omental pregnancy after in vitro fertilization complicated by hemoperitoneum-how to manage it laparoscopically.

OBJECTIVE: To report an uncommon case of primary OP treated laparoscopically. Ectopic pregnancy (EP) is the leading cause of maternal mortality during the first trimester and the incidence increases with assisted reproductive techniques, occurring in approximately 1.5%-2.1% of patients undergoing in vitro fertilization.1 Omental pregnancy (OP) is an extremely rare form of EP accounting for less than 1% of all EPs. OP can be classified as primary or secondary on the basis of Studdiford's criteria2. The preoperative diagnosis of OP is complex and usually occur in acute circumstances during a throughout intraoperative evaluation of the abdomen.3-5 A delayed diagnosis poses a serious threat to the survival of the patient; therefore, it is important to remark that EP can exist in unusual locations and prompt surgical intervention may be necessary. DESIGN: A step-by-step narrated video of a rare clinical case and description of the surgical procedure. SETTING: Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero - Universitaria di Bologna" Bologna, Italy. PATIENT: A 36-year-old woman was referred to our emergency room because of acute abdominal pain and nausea for 2 hours with no signs of hemodynamic instability. The patient also complained that poor vaginal bleeding appeared during the last 24 hours. The patient has undergone a cycle of in vitro fertilization with an elective single frozen embryo transfer of a blastocyst on day 5, 2 months before. She had no relevant clinical or surgical history. Diffuse abdominal tenderness and a painful uterus at mobilization were appreciated at clinical examination. A massive hemoperitoneum was diagnosed using transvaginal-transabdominal ultrasound, and no uterine or adnexal lesions were identified. The ß-human chronic gonadotropin level was 43.861 mIU/mL, and the hemoglobin value was 10.5 g/dL. INTERVENTIONS: On suspicion of a ruptured EP, after detailed counseling and the acquisition of informed consent, a laparoscopic exploration was planned. First, the hemoperitoneum was evacuated to allow visualization of the abdominal cavity. At pelvic inspection, no EP was found. Throughout the exploration of the abdominal cavity, a 4-cm bluish cystic mass of friable consistency was detected infiltrating the omentum and the mesentery. According to Studdiford's criteria, the diagnosis of a primary OP was established. A careful and complete excision of the ectopic implant was performed with an ultrasonic system and required a considerable hemostatic effort using bipolar energy, endoscopic clips, and mechanical compression. The postoperative course was uneventful. The ß-human chronic gonadotropin levels gradually decreased to negative values within 29 days after surgery. MAIN OUTCOME MEASURE(S): Omental ectopic pregnancy can be successfully managed with a laparoscopic approach even in an emergency setting. CONCLUSION: Omental pregnancy can easily be overlooked, even by skilled surgeons, during laparoscopic exploration. It is mandatory that all peritoneal surfaces and the omentum be carefully inspected during surgery in patients without other signs of pelvic EP.We confirm that the patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites.

Pathologic maternal and neonatal outcomes associated with programmed embryo transfer.

PURPOSE: In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal pregnancy outcomes associated with programmed embryo transfer cycles. We next consider whether these pathological pregnancy outcomes might be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation. Finally, in the second companion article, we explore potential etiologies and suggest strategies for prevention. METHODS: Comprehensive review of primary literature. RESULTS: The preponderance of retrospective and prospective observational studies suggests that increased risk for hypertensive disorders of pregnancy (HDP) and preeclampsia in assisted reproduction involving autologous embryo transfer is associated with programmed cycles. For autologous frozen embryo transfer (FET) and singleton live births, the risk of developing HDP and preeclampsia, respectively, was less for true or modified natural and stimulated cycles relative to programmed cycles: OR 0.63 [95% CI (0.57-0.070)] and 0.44 [95% CI (0.40-0.50)]. Though data are limited, the classification of preeclampsia associated with programmed autologous FET was predominantly late-onset or term disease. Other adverse pregnancy outcomes associated with autologous FET, especially programmed cycles, included increased prevalence of large for gestational age infants and macrosomia, as well as higher birth weights. In one large registry study, FET was associated with fetal overgrowth of a symmetrical nature. Postterm birth and placenta accreta not associated with prior cesarean section, uterine surgery, or concurrent placenta previa were also associated with autologous FET, particularly programmed cycles. The heightened risk of these pathologic pregnancy outcomes in programmed autologous FET does not appear to be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation, although the latter may contribute a modest degree of increased risk for fetal overgrowth and perhaps HDP and preeclampsia in FET irrespective of the endometrial preparation. CONCLUSIONS: Programmed autologous FET is associated with an increased risk of several, seemingly diverse, pathologic pregnancy outcomes including HDP, preeclampsia, fetal overgrowth, postterm birth, and placenta accreta. Though the greater risk for preeclampsia specifically associated with programmed autologous FET appears to be well established, further research is needed to substantiate the limited data currently available suggesting that the classification of preeclampsia involved is predominately late-onset or term. If substantiated, then this knowledge could provide insight into placental pathogenesis, which has been proposed to differ between early- and late-onset or term preeclampsia (see companion paper for a discussion of potential mechanisms). If a higher prevalence of preeclampsia with severe features as suggested by some studies is corroborated in future investigations, then the danger to maternal and fetal/neonatal health is considerably greater with severe disease, thus increasing the urgency to find preventative measures. Presupposing significant overlap of these diverse pathologic pregnancy outcomes within subjects who conceive by programmed embryo transfer, there may be common etiologies.

Indications affect neonatal outcomes following early rescue ICSI: a retrospective study.

PURPOSE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients. CONCLUSION: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.

Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study.

OBJECTIVES: We aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: A retrospective cohort study. SETTING: Data were collected from a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS: This study included 17 419 eligible women aged ≤40 years who underwent the first IVF/ICSI cycles from January 2015 to December 2021. Women were divided into three groups according to their AAM: ≤12 years (n=5781), 13-14 years (n=9469) and ≥15 years (n=2169). RESULTS: The means of age at recruitment and AAM were 30.4 years and 13.1 years, respectively. Restricted cubic spline models suggested that early menarche age increased the risk of OHSS. The multivariable logistic analysis showed that women with menarche age ≤12 years were more likely to suffer from OHSS (OR 1.321, 95% CI 1.113 to 1.567) compared with those aged 13-14 years among the whole cohort. This significant relationship remained in women administered with different ovarian stimulation protocols and gonadotrophin doses. When stratified by female age, this correlation was presented only in patients aged ≤30 years (OR 1.362, 95% CI 1.094 to 1.694). And the mediation analysis showed that the relationship between AAM and OHSS was totally mediated by antral follicle counts (AFC). CONCLUSION: Menarche age earlier than 12 years may increase the OHSS risk in women aged ≤30 years through the mediation of AFC. More prospective studies are required to verify the results.

Association of duration of embryo culture with risk of large for gestational age delivery in cryopreserved embryo transfer cycles.

OBJECTIVE: To examine the relationship between the day of embryo cryopreservation and large for gestational age (LGA) infants in women undergoing frozen embryo transfers (FETs) after cryopreservation on days 2-7 after fertilization and to compare the risk of the day of embryo cryopreservation to other possible risk factors of LGA after FET cycles. DESIGN: Retrospective cohort study. SETTING: Society of Assisted Reproduction Clinical Outcomes Reporting System. PATIENTS: Women undergoing FET cycles. INTERVENTION: Day of cryopreservation. MAIN OUTCOME MEASURE: Singleton LGA infant. RESULTS: A total of 33,030 (18.2%) FET cycles in the study group (n = 181,592) resulted in LGA infants during the study period of 2014-2019. There was an increase in LGA risk when cryopreservation was performed from day 2 (13.7%) to days 3-7 (14.4%, 15.0%, 18.2%, 18.5%, and 18.9%). In the log-binomial model, the risk increased compared with days 2-3 combined when cryopreservation was performed on days 5-7 (adjusted relative risk [aRR] 1.32, 95% confidence interval [CI] 1.22-1.44 for day 5, aRR 1.34, 95% CI 1.23-1.46 for day 6, and aRR 1.42, 95% CI 1.25-1.61 for day 7). Other factors most associated with LGA risk in the log-binomial model were preterm parity of >3 compared with 0 (aRR 1.82, 95% CI 1.24-2.69) and body mass index (BMI) of >35 kg/m2 compared with normal weight (aRR 1.94, 95% CI 1.88-2.01). Increasing gravity, parity, BMI, number of oocytes, and embryo grade were also associated with LGA in this model. Asian, Black, Hispanic, and combined Hawaiian and Pacific Islander were protective factors in the model compared with White patients. Low BMI (<18.5 kg/m2) was also considered a protective factor in the model compared with normal BMI. CONCLUSION: Duration of embryo culture was associated with an increased risk of LGA in this study cohort when controlling for known confounders such as maternal BMI and parity. This study sheds new light on the possible link between FET and LGA infants.

International gestational surrogacy in the United States, 2014-2020.

OBJECTIVE: To describe characteristics, trends, and outcomes of international gestational surrogacy cycles in the United States (US). DESIGN: Retrospective cohort study. SETTING: All assisted reproductive technology cycles in the US reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting Systems that included an embryo transfer to a gestational carrier from 2014 to 2020. PATIENTS: International vs. US intended parents. MAIN OUTCOME MEASURES: Cycle characteristics, geographic distributions, and obstetrical outcomes. RESULTS: Of 40,177 embryo transfers to a gestational carrier from 2014 to 2020, 32% were for international intended parents. The number and percent of international intended parents' gestational carrier cycles increased each year from 2014 (n = 2758, 22.0%) to 2019 (n = 4905, 39.8%) with a decrease in 2020 (n = 4713, 31.8%). Compared with cycles for US intended parents, there was a larger decrease in gestational carrier cycles between 2019 and 2020 for international intended parents (3.9% vs. 32.2%). International intended parents were more likely to be male sex (41.3% vs. 19.6%), older than 42 years (33.9% vs. 26.2%) and identify as Asian race (65.6% vs. 16.5%). International intended parents were largely from China (41.7%), followed by France (9.2%) and Spain (8.5%). Gestational carriers for international intended parents were more commonly younger than 30 years (42.8% vs. 29.1%) and identified as Hispanic race (28.6% vs. 11.7%) compared with gestational carriers for US intended parents. Cycles with international intended parents were more likely to use donor eggs (67.1% vs. 43.5%), intracytoplasmic sperm injection (72.8% vs. 55.4%), and preimplantation genetic testing (79.0% vs. 55.8%). Cycles with international and US intended parents had similar obstetrical outcomes, including live birth (adjusted risk ratio 1.01, 95% confidence interval 1.00-1.03) and multiple pregnancy (adjusted risk ratio 1.00, 95% confidence interval 0.94-1.06) rates. CONCLUSION: An increasing number of international intended parents are utilizing gestational surrogacy in the US and more frequently using cost-enhancing specialized treatment techniques. This increase is potentially because of restrictive international commercial surrogacy laws and the increased availability of reproductive medical expertise. Given this growing demographic, continued examination of the volume of cross-border reproductive treatment, as well as the legal and ethical considerations, is warranted.

Chapter 11. Endometriosis-related complications in women undergoing in-vitro fertilization.

As a chronic inflammatory disease, endometriosis generates fibrosis and anatomic distortion, which add extra-challenges to assisted reproductive technology cycles and requires a personalized approach. Patients with endometriomas have significantly decreased ovarian reserve and the ultrasound examination tends to be challenging, possibly underestimating follicle counts. It is crucial to assess the feasibility of oocyte retrieval procedure during the initial examination of the patient, as the distortion of the pelvic anatomy, the presence of hydrosalpinges and endometriomas might render the procedure difficult and increase the risk of complications. Possible injury to adjacent organs and risk of infection must be considered. Assisted reproductive technology seems to have limited or no impact on endometriosis recurrence, pain symptom progression or the size of endometrioma.

Development of a single-visit protocol for the management of pregnancy of unknown location following in vitro fertilization: a retrospective study.

STUDY QUESTION: Can women with pregnancy of unknown location (PUL) following in vitro fertilization (IVF) be risk-stratified regarding the subsequent need for medical intervention, based on their demographic characteristics and the results of serum biochemistry at the initial visit? SUMMARY ANSWER: The ratio of serum hCG to number of days from conception (hCG/C) or the initial serum hCG level at ≥5 weeks' gestation could be used to estimate the risk of women presenting with PUL following IVF and needing medical intervention during their follow-up. WHAT IS KNOWN ALREADY: In women with uncertain conception dates presenting with PUL, a single serum hCG measurement cannot be used to predict the final pregnancy outcomes, thus, serial levels are mandatory to establish a correct diagnosis. Serum progesterone levels can help to risk-stratify women at their initial visit but are not accurate in those taking progesterone supplementation, such as women pregnant following IVF. STUDY DESIGN, SIZE, DURATION: This was a retrospective study carried out at two specialist early pregnancy assessment units between May 2008 and January 2021. A total of 224 women met the criteria for inclusion, but 14 women did not complete the follow-up and were excluded from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We selected women who had an IVF pregnancy and presented with PUL at ≥5 weeks' gestation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 30/210 (14.0%, 95% CI 9.9-19.8) women initially diagnosed with PUL required surgical intervention. The hCG/C was significantly higher in the group of women requiring an intervention compared to those who did not (P = 0.003), with an odds ratio of 3.65 (95% CI 1.49-8.89, P = 0.004). A hCG/C <4.0 was associated with a 1.9% risk of intervention, which accounted for 25.7% of the study population. A similar result was obtained by substituting hCG/C <4.0 with an initial hCG level <100 IU/l, which was associated with 2.0% risk of intervention, and accounted for 23.8% of the study population (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is that it is retrospective in nature, and as such, we were reliant on existing data. WIDER IMPLICATIONS OF THE FINDINGS: A previous study in women with PUL after spontaneous conception found that a 2% intervention rate was considered low enough to eliminate the need for close follow-up and serial blood tests. Using the same 2% cut-off, a quarter of women with PUL after IVF could also avoid attending for further visits and investigations. STUDY FUNDING/COMPETING INTEREST(S): No external funding was required for this study. No conflicts of interest are required to be declared. TRIAL REGISTRATION NUMBER: N/A.

Unhealthy air quality secondary to wildfires is associated with lower blastocyst yield.

OBJECTIVE: To study the impact of unhealthy air quality from the 2020 Oregon wildfires on outcomes for patients undergoing in vitro fertilization (IVF) treatment. DESIGN: A retrospective cohort study. SETTING: A university-based fertility clinic. PATIENTS: Subjects were undergoing IVF treatment from the 6 weeks preceding the wildfires through a 10-day exposure period. Cohorts were classified on the basis of whether subjects experienced patient and/or laboratory exposure to unhealthy air quality. Patient exposure was defined as at least 4 days of ovarian stimulation overlapping with the exposure, and laboratory exposure was defined as at least 2 days of IVF treatment and embryogenesis overlapping with the exposure. The unexposed cohort consisted of remaining subjects without defined exposure, with cycles in the 6 weeks preceding the wildfires. As some subjects had dual exposure and appeared in both patient and laboratory exposure cohorts, each cohort was separately compared with the unexposed control cohort. INTERVENTION: A 10-day period of unhealthy air quality caused by smoke plumes from a wildfire event. MAIN OUTCOME MEASURES: The primary outcome was the blastulation rate. Secondary outcomes included fertilization rate, number of blastocysts obtained, and cycles with no blastocysts frozen or transferred. RESULTS: Sixty-nine subjects underwent ovarian stimulation and IVF treatment during the 6 weeks preceding the wildfires through the 10-day period of unhealthy air quality. Of these, 15 patients were in the laboratory exposure cohort, 16 were in the patient exposure cohort, and 44 were unexposed. Six subjects appeared in both laboratory and patient exposure cohorts. Although neither exposure cohort had significantly decreased blastulation rate compared with the unexposed, the median number of blastocysts obtained was significantly lower in the laboratory exposure cohort than the unexposed group (2 [range 0-14] vs. 4.5 [range 0-21], respectively). The laboratory exposure cohort had significantly more cycles with no blastocysts obtained (3/15 [20%] vs. 1/44 [2%]). There were no significant differences in IVF treatment outcomes between patient exposure and unexposed cohorts. These findings persisted after controlling for age. There were no significant differences in pregnancy outcomes observed after embryo transfer between the exposure group and the unexposed group. CONCLUSION: For a cohort of patients undergoing IVF treatment, an acute episode of outside wildfire smoke exposure during fertilization and embryogenesis was associated with decreased blastocyst yield.

Iatrogenic and demographic determinants of the national plural birth increase.

OBJECTIVE: To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF), and unassisted conception to the increase in national plural births in the United States, a significant contributor to adverse maternal and infant health outcomes. DESIGN: National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the United States) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966 and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts. RESULT(S): From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1,000 live births), then declined to 31.2/1,000 live births; the triplet and higher order birth rate increased 6.7-fold to a 1998 high (1.9/1,000 live births), then declined to 0.8/1,000 live births. In 2021, the contribution of unassisted conception among women aged <35 years to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women aged ≥35 years (16.8%), and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women aged <35 and ≥35 years has increased, and the contribution of IVF has decreased. CONCLUSION(S): Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age of ≥35 years is a significant contributor to the national plural birth increase.

Sperm DNA fragmentation index affect pregnancy outcomes and offspring safety in assisted reproductive technology.

The role of sperm DNA fragmentation index (DFI) in investigating fertility, embryonic development, and pregnancy is of academic interest. However, there is ongoing controversy regarding the impact of DFI on pregnancy outcomes and the safety of offspring in the context of Assisted Reproductive Technology (ART). In this study, we conducted an analysis of clinical data obtained from 6330 patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at the reproductive medical center of The First People's Hospital of Shangqiu and The Affiliated Hospital of Zhengzhou University. The patients was stratified into two distinct groups: IVF group and ICSI group, Within each group, patients were further classified into three subgroups. IVF: group A (< 15%) included 3123 patients, group B (15-30%) included 561 patients, and group C (≥ 30%) included 46 patients. ICSI: group A (< 15%) included 1967 patients, group B (15-30%) included 462 patients, and group C (≥ 30%) included 171 patients. Data were collected and subjected to statistical analysis. There were no significant differences in the basic characteristics among the three groups, and the sperm DFI did not significantly affect the fertilization rates, pregnancy rates, stillbirth rates and the number of birth defects. However, the incidences of miscarriage rates in IVF/ICSI groups with DFI > 30% and DFI 15-30% were significantly higher than those in IVF/ICSI groups with DFI < 15%, and the miscarriage rates in ICSI group with DFI > 30% were significantly higher than DFI 15-30% group, the smooth fitting curve shows that there is a positive correlation between miscarriage rates and sperm DFI (OR 1.095; 95% CI 1.068-1.123; P < 0.001). The birth weight of infants in the IVF/ICSI groups with DFI > 30% and DFI 15-30% exhibited a statistically significant decrease compared to those in the IVF/ICSI groups with DFI < 15%. Furthermore, the birth weight of infants in the ICSI group with DFI > 30% was lower than that of the DFI 15-30% group. The smooth fitting curve analysis demonstrates a negative association between birth weight and sperm DFI (OR 0.913; 95% CI 0.890-0.937; P < 0.001). Sperm DFI has an impact on both miscarriage rates and birth weight in assisted reproductive technology. The smooth fitting curve analysis reveals a positive correlation between miscarriage rates and DFI, while a negative correlation is observed between birth weight and DFI.

Risk factors of ectopic pregnancy after in vitro fertilization-embryo transfer in Chinese population: A meta-analysis.

BACKGROUND: The prevalence of ectopic pregnancy after assisted reproduction is notably high, posing a significant threat to the life safety of pregnant women. Discrepancies in published results and the lack of a comprehensive description of all risk factors have led to ongoing uncertainties concerning ectopic pregnancy after assisted reproduction. OBJECTIVE: This study aimed to understand the risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population and provide a reference for targeted prevention and treatment. METHODS: A comprehensive search of the China National Knowledge Infrastructure, Wang fang Database, China Science Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Web of Science, and Embase was conducted to identify relevant literature on the risk factors for ectopic pregnancy in Chinese women after assisted reproductive technology in Chinese women. A meta-analysis of the included studies was performed using Stata17. RESULTS: Overall, 34 articles were included in the analysis. The risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population included a thin endometrium on the day of HCG administration and embryo transplantation, a history of ectopic pregnancy, secondary infertility, a history of induced abortion, polycystic ovary syndrome, decreased ovarian reserve, tubal factor infertility, cleavage stage embryo transfer, fresh embryo transfer, artificial cycle protocols, elevated estradiol levels on the day of human chorionic gonadotropin administration, a history of tubal surgery, two or more number of embryo transfers, previous pregnancy history, and a history of pelvic surgery. CONCLUSION: This study clarified the factors influencing ectopic pregnancy after in vitro fertilization and embryo transfer in the Chinese population, focusing on high-risk groups. Targeted and personalized intervention measures should be adopted to prevent and detect the disease early to reduce its incidence and harm. TRIAL REGISTRATION: The protocol for this view was registered in PROSPERO (CRD42023414710).

Do we overlook predictive factors in Poseidon 1 patients? A retrospective analysis co-evaluating antral follicle counts & diameters.

BACKGROUND: An unexpected impaired ovarian response pertains to an insufficient reaction to controlled ovarian hyperstimulation. This deficient reaction is identified by a reduced count of mature follicles and retrieved oocytes during an IVF cycle, potentially diminishing the likelihood of a successful pregnancy. This research seeks to examine whether the characteristics of antral follicles can serve as predictive indicators for the unexpected impaired ovarian response to controlled ovarian stimulation (COS). METHODS: This retrospective cohort study was conducted at a tertiary university hospital. The electronic database of the ART (assisted reproductive technologies) center was screened between the years 2012-2022. Infertile women under 35 years, with normal ovarian reserve [anti-Müllerian hormone (AMH) > 1.2 ng/ml, antral follicle count (AFC) > 5] who underwent their first controlled ovarian stimulation (COS) cycle were selected. Women with < 9 oocytes retrieved (group 1 of the Poseidon classification) constituted the group A, whereas those with ≥ 9 oocytes severed as control (normo-responders) one (group B). Demographic, anthropometric and hormonal variables together with COS parameters of the two groups were compared. RESULTS: The number of patients with < 9 oocytes (group A) was 404, and those with ≥ 9 oocytes were 602 (group B). The mean age of the group A was significantly higher (30.1 + 2.9 vs. 29.4 + 2.9, p = 0.01). Group A displayed lower AMH and AFC [with interquartile ranges (IQR); AMH 1.6 ng/ml (1-2.6) vs. 3.5 ng/ml (2.2-5.4) p < 0.01, AFC 8 (6-12) vs. 12 (9-17), p < 0.01]. The number of small antral follicles (2-5 mm) of the group A was significantly lower [6 (4-8) vs. 8 (6-12) p < 0.01), while the larger follicles (5-10 mm) remained similar [3 (1-5) vs. 3(1-6) p = 0.3] between the groups. CONCLUSION: The propensity of low ovarian reserve and higher age are the main risk factors for the impaired ovarian response. The proportion of the small antral follicles may be a predictive factor for ovarian response to prevent unexpected poor results.

Isthmocele, not cesarean section per se, reduces in vitro fertilization success: a systematic review and meta-analysis of over 10,000 embryo transfer cycles.

IMPORTANCE: Previous reviews have shown that a history of cesarean section (CS) is associated with a worse in vitro fertilization (IVF) prognosis. To date, whether the decline in the IVF chances of success should be attributed to the CS procedure itself or to the presence of isthmocele remains to be clarified. OBJECTIVE: To summarize the available evidence regarding the impact of isthmocele on IVF outcomes. DATA SOURCES: Electronic databases and clinical registers were searched until May 30, 2023. STUDY SELECTION AND SYNTHESIS: Observational studies were included if they assessed the effect of isthmocele on IVF outcomes. Comparators were women with isthmocele and women without isthmocele with a previous CS or vaginal delivery. Study quality was assessed using the modified Newcastle-Ottawa Scale. MAIN OUTCOMES: The primary outcome was the live birth rate (LBR). The effect measures were expressed as adjusted odds ratios (aORs) and unadjusted odds ratios (uORs) with 95% confidence intervals (95% CIs). The body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation working group methodology. RESULTS: Eight studies (n = 10,873 patients) were included in the analysis. Women with isthmocele showed a lower LBR than both women with a previous CS without isthmocele (aOR, 0.62; 95% CI, 0.53-0.72) and those with a history of vaginal delivery (aOR, 0.55; 95% CI, 0.42-0.71). The LBRs in women with a previous CS without isthmocele and those with a history of vaginal delivery were similar (aOR, 0.74; 95% CI, 0.47-1.15). Subgroup analysis suggested a negative effect of the intracavitary fluid (ICF) in women with isthmocele on the LBR (uOR, 0.36; 95% CI, 0.18-0.75), whereas the LBRs in women without ICF and those without isthmocele were similar (uOR, 0.94; 95% CI, 0.61-1.45). CONCLUSION AND RELEVANCE: We found moderate quality of evidence (Grading of Recommendations Assessment, Development and Evaluation grade 3/4) supporting a negative impact of isthmocele, but not of CS per se, on the LBR in women undergoing IVF. The adverse effect of isthmocele on IVF outcomes appears to be worsened by ICF accumulation before embryo transfer. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023418266.

Higher live birth rates are associated with a normal body mass index in preimplantation genetic testing for aneuploidy frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To determine whether body mass index (BMI) was associated with live birth in patients undergoing transfer of frozen-thawed preimplantation genetic testing for aneuploidy (PGT-A) embryos. DESIGN: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. SUBJECTS: All autologous and donor recipient PGT-A-tested cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to 2017. INTERVENTION(S): Body mass index. MAIN OUTCOME MEASURE(S): The primary outcome measure was the live birth rate, and the secondary outcome measures were the clinical pregnancy and biochemical pregnancy rates. Multivariable generalized additive mixed models and log-binomial models were used to model the relationship between BMI and outcome measures. RESULT(S): A total of 77,018 PGT-A cycles from 55,888 patients were analyzed. Of these cycles, 70,752 were autologous, and 6,266 were donor recipient. In autologous cycles, a statistically significant and clear nonlinear relationship was observed between the BMI and live birth rates, with the highest birth rates observed for the BMI range of 23-24.99 kg/m2. When using 23-24.99 kg/m2 as the referent, other BMI ranges demonstrated a lower probability of live birth and clinical pregnancy that continued to decrease as the BMI moved further from the reference value. Patients with a BMI of <18.5 kg/m2 had a 11% lower probability of live birth, whereas those with a BMI of ≥40 kg/m2 had a 27% lower probability than the referent. CONCLUSION(S): A normal-weight BMI range of 23-24.99 kg/m2 was associated with the highest probability of clinical pregnancy and live birth after a frozen-thawed PGT-A-tested blastocyst transfer in both autologous and donor recipient cycles. A BMI outside the range of 23-24.99 kg/m2 is likely associated with a malfunction in the implantation process, which is presumed to be related to a uterine factor and not an oocyte factor, as both autologous and donor recipient cycle outcomes were associated similarly with the BMI of the intended parent.

Increasing Endometrial Thickness Beyond 8 mm Does Not Alter Clinical Pregnancy Rate After Single Euploid Embryo Transfer.

The aim of this study was to investigate if variation in endometrial thickness affects clinical pregnancy and live birth rates among patients undergoing single euploid embryo transfer (SET). A retrospective review of IVF cycles performed at a single private fertility institution between 2015 and 2020 was performed. Patients with normal uterine anatomy undergoing their first SET of a euploid embryo undergoing their first cycle at the center were included, for a total of 796 cycles. Endometrial thickness was measured by transvaginal ultrasound following 10-14 days of estradiol exposure. Specific infertility diagnoses did not significantly impact endometrial lining thickness with means across diagnoses ranging from 9.3 to 11.0 mm. Endometrial thickness was grouped into five categories: < 8 mm, 8-10 mm, 10-13 mm, 13-15 mm, and ≥ 15 mm. Using 8-10 mm as the reference group, the odds ratio of live birth was 0.5, 1.22, 1.05, and 1.05 for < 8 mm, 10-13 mm, 13-15 mm, and ≥ 15 mm groups, respectively. Risk of first trimester miscarriage was equivalent across groups. There was a trend toward an increased rate of biochemical pregnancies in patients with a < 8 mm and ≥ 15 mm endometrium; however, this was not statistically significant. The clinical pregnancy and live birth rate were lowest in patients with < 8-mm endometrial thickness. For single euploid embryo transfers, an endometrial lining greater than or equal to 8 mm confers optimal live birth rates following a medicated FET cycle. These data confirm the findings of prior studies in fresh embryo transfers without the confounders of supraphysiologic ovarian hormone concentrations and genetically untested embryos.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis.

OBJECTIVE: To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. DESIGN: Retrospective cohort study. SETTING: Donor Egg Bank Database. PATIENTS: Patients undergoing in vitro fertilization using vitrified donor oocytes from 35 in vitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. INTERVENTION: Oocyte donor-recipient cycles. MAIN OUTCOME MEASURES: Ongoing pregnancy rate (OPR) per ET. RESULTS: A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). CONCLUSION: This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).