Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles.

BACKGROUND: Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle. METHODS: This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021. RESULTS: There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86-1.02, adjusted OR 0.97, 95%CI 0.89-1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53-0.99, adjusted OR 0.74, 95% CI 0.53-1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI. CONCLUSIONS: In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Effect of Day 3 cell number on the live birth rate of vitrified-warmed Day 5 single blastocyst transfer in young women.

BACKGROUND: Previous studies have reported inconsistent results regarding blastocyst selection with a high day 3 (D3) cell number and the eventual pregnancy outcomes. Thus, in this study, the relationship between the D3 cell number and clinical outcomes of day 5 single blastocyst transfer (SBT) in vitrified-warmed transfer cycles was investigated. METHODS: Our retrospective study included 1144 day 5 SBT in vitrified-warmed cycles between February 2016 and February 2021. All cycles were the first vitrified-warmed cycles, and the female patients were less than 35 years of age. Based on the D3 cell number, the cycles were divided into four groups, as follows: group A (3-7 cells, n = 130); group B (8-9 cells, n = 621); group C (10-12 cells, n = 328); and group D (13-16 cells, n = 65). The differences in the live birth rate (LBR), clinical pregnancy rate, and miscarriage rate were examined among the four groups. RESULTS: The LBR and clinical pregnancy rate increased with the D3 cell number (P < 0.01). No significant difference was found in the miscarriage rate among the groups (P = 0.055). After adjusting for confounding factors, the LBR was significantly higher in groups C (odds ratio [OR] = 1.477, 95% confidence interval [CI]: 1.124-1.941, P = 0.005) and D (OR = 2.000, 95% CI: 1.166-3.429, P = 0.012) than in group B. CONCLUSIONS: A high D3 cell number (> 9 cells) was associated with a high LBR in the vitrified-warmed day 5 SBT cycles of patients < 35 years of age. The cell number of D3 embryos can be an important reference indicator for blastocyst selection. Among blastocysts with the same morphological score, those with > 9 cells on D3 can be preferentially selected for transplantation.

Comparison of pregnancy outcomes among patients of different ages who underwent frozen-thawed high-quality single blastocyst transfer.

OBJECTIVE: To investigate the feasibility of performing frozen-thawed high-quality single blastocyst transfer in women of different ages. METHODS: A total of 1,279 women were divided into four groups: a 38-40-year-old group (n = 147), 35-37-year-old group (n = 164), 30-34-year-old group (n = 483), and < 30-year-old group (n = 485). Intergroup comparisons of baseline characteristics and pregnancy and neonatal outcomes were made. RESULTS: The clinical pregnancy rate (47.6%), and live birth rate (34.0%) in the 38-40-year-old group were significantly lower than those in the 30-34-year-old group (64.4%, 50.9%, respectively; all P < 0.001) and < 30-year-old group (62.9%, 50.7%, respectively; all P < 0.001). However, the 35-37-year-old group did not differ from the other three groups in these two dimensions (all P > 0.05). Moreover, there were no differences in the rates of biochemical pregnancy, miscarriage, or obstetric or neonatal complications among the four groups (all P > 0.05). According to the multivariate logistic regression analysis, the 35-37-year-old group was not associated with non-live birth outcomes, adverse pregnancy outcomes, or obstetric or neonatal complications. However, being 38-40 years of age was a risk factor for non-live birth (OR = 2.121, 95% CI: 1.233-3.647) and adverse pregnancy outcomes (OR = 1.630, 95% CI: 1.010-2.633). Post hoc power analysis showed that the study was sufficiently powered to detect meaningful differences. CONCLUSION: Frozen-thawed high-quality single blastocyst transfer produces the same satisfactory pregnancy outcomes for women aged 35-37 years as younger patients. Future prospective randomized controlled studies with larger populations are needed to verify the feasibility and safety of this method.

Effects of hysteroscopic septum incision versus expectant management on IVF outcomes in women with complete septate uterus: a retrospective study.

OBJECTIVE: This retrospective study aimed to assess the impact of hysteroscopic septum incision on in vitro fertilization (IVF) outcomes among infertile women diagnosed with a complete septate uterus and no history of recurrent pregnancy loss. METHODS: The study was conducted at a tertiary reproductive center affiliated with a university hospital and involved 78 women with a complete septate uterus. Among them, 34 women underwent hysteroscopic septum incision, while 44 women opted for expectant management. The primary outcome measure was the live birth rate, while secondary outcomes included clinical pregnancy rate, preterm birth rate, miscarriage rate, and ongoing pregnancy rate. RESULTS: Women who underwent hysteroscopic septum incision demonstrated a comparable likelihood of achieving a live birth compared to those managed expectantly (25% vs. 25%, Relative Risk (RR): 1.000, 95% Confidence Interval (CI): 0.822 to 1.216). No preterm births occurred in either group. The clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate showed no significant differences between the surgical group and the expectant management group. Subgroup analyses based on the type of embryo transferred also revealed no significant differences in outcomes. CONCLUSIONS: Hysteroscopic septum incision does not appear to yield improved IVF outcomes compared to expectant management in infertile women with a complete septate uterus and no history of recurrent pregnancy loss.

Establishment and validation of a nomogram for subsequent first-cycle live births in patients diagnosed with recurrent implantation failure: a population-based analysis.

Background: The inability of patients with recurrent implantation failure (RIF) to achieve pregnancy and a live birth after multiple high-quality embryo transfer treatments has been recognized as a major obstacle to successful application of artificial reproductive technologies. The objective of this study was to establish and validate a nomogram for prediction of subsequent first-cycle live births to guide clinical practice in patients diagnosed with RIF. Methods: A total of 538 patients who underwent in vitro fertilization/intracytoplasmic sperm injection treatment and were first diagnosed with RIF at the Reproductive Center of the First Affiliated Hospital of Xinjiang Medical University between January 2017 and December 2020 were enrolled. The patients were randomly divided into a training cohort (n=408) and a validation set (n=175) in a ratio of 7:3. A nomogram model was constructed using the training set based on the results of univariate and multivariate logistic regression analyses and validated in the validation set. Results: Age, body mass index, duration of RIF, endometrial thickness, type of embryo transferred, and number of previous biochemical pregnancies were included in the nomogram for prediction of subsequent first-cycle live births in patients diagnosed with RIF. Analysis of the area under the receiver-operating characteristic curve, calibration plots, and decision curve analysis showed that our predictive model for live births had excellent performance. Conclusion: We have developed and validated a novel predictive model that estimates a woman's chances of having a live birth after a diagnosis of RIF and provides clinicians with a personalized clinical decision-making tool.

Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy among the multiple causes of death on the death certificate. The frequencies of major cause-of-death categories among deaths of female patients aged 15 to 44 years, maternal deaths, deaths due to obstetrical causes (ie, direct obstetrical deaths), and deaths due to maternal medical conditions aggravated by pregnancy or its management (ie, indirect obstetrical deaths) were quantified. RESULTS: Maternal deaths, per National Vital Statistics System methodology, increased by 144% (95% confidence interval, 130-159) from 9.65 in 1999-2002 (n=1550) to 23.6 per 100,000 live births in 2018-2021 (n=3489), with increases occurring among all race and ethnicity groups. Direct obstetrical deaths increased from 8.41 in 1999-2002 to 14.1 per 100,000 live births in 2018-2021, whereas indirect obstetrical deaths increased from 1.24 to 9.41 per 100,000 live births: 38% of direct obstetrical deaths and 87% of indirect obstetrical deaths in 2018-2021 were identified because of a positive pregnancy checkbox. The pregnancy checkbox was associated with increases in less specific and incidental causes of death. For example, maternal deaths with malignant neoplasms listed as a multiple cause of death increased 46-fold from 0.03 in 1999-2002 to 1.42 per 100,000 live births in 2018-2021. Under the alternative formulation, the maternal mortality rate was 10.2 in 1999-2002 and 10.4 per 100,000 live births in 2018-2021; deaths from direct obstetrical causes decreased from 7.05 to 5.82 per 100,000 live births. Deaths due to preeclampsia, eclampsia, postpartum hemorrhage, puerperal sepsis, venous complications, and embolism decreased, whereas deaths due to adherent placenta, renal and unspecified causes, cardiomyopathy, and preexisting hypertension increased. Maternal mortality increased among non-Hispanic White women and decreased among non-Hispanic Black and Hispanic women. However, rates were disproportionately higher among non-Hispanic Black women, with large disparities evident in several causes of death (eg, cardiomyopathy). CONCLUSION: The high and rising rates of maternal mortality in the United States are a consequence of changes in maternal mortality surveillance, with reliance on the pregnancy checkbox leading to an increase in misclassified maternal deaths. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows lower, stable maternal mortality rates and declines in maternal deaths from direct obstetrical causes.

The use of immunomodulation therapy in women with recurrent implantation failure undergoing assisted conception: A multicentre cohort study.

PROBLEM: Recurrent implantation failure (RIF) after multiple embryo transfers remains a vexing problem and immunomodulators have been used with conflicting results. This study aims to assess the effect of immunomodulation therapy on live birth rate (LBR) in women with RIF undergoing assisted reproduction treatment (ART). METHOD OF STUDY DESIGN: This is a retrospective cohort study in multicentre network of private assisted conception units in the UK. The study included women who had at least two failed attempts of embryo transfers at CARE fertility network in the period from 1997 to 2018. Women in the treatment group had immunomodulator drugs in the form of corticosteroids, low molecular weight heparin (LMWH), and intravenous intralipid (IVIL) infusions, either separately or in combination, after immunological testing, in addition to standard ART whilst women in the control group had only ART without immunomodulators. The primary outcome was LBR per cycle. Secondary outcomes included the rates of clinical pregnancy (CPR), cumulative live birth (CLBR), and miscarriage. RESULTS: A total of 27 163 ART cycles fulfilled the inclusion criteria, of which 5083 had immunomodulation treatment in addition to standard ART treatment, and 22 080 had standard ART treatment alone. Women in the treatment group were significantly older (mean age 38.5 vs. 37.1 years, p < .001), and had a higher number of previous failed ART cycles (mean 4.3 vs. 3.8, p < .01). There was a higher LBR in women who received immunomodulation therapy when compared with the control group (20.9% vs. 15.8%, odds ratio [OR] 1.4, 95% confidence interval [CI] 1.29-1.53, p < .001). Multivariate regression analysis showed that immunomodulation treatment was a significant independent predictor of live birth after adjusting for other confounders (adjusted OR [aOR] 1.33, 95% CI 1.15-1.54, p < .001). Survival analysis showed a higher CLBR in the treatment group (adjusted hazard ratio [aHR] 1.78, 95% CI 1.62-1.94, p < .001). CONCLUSION(S): This study provides evidence of a potential beneficial effect of immunomodulation therapy in women with RIF after immunological testing. There remains a need for high quality, adequately powered multicentre RCTs to robustly address the role of immunomodulation in women with RIF. There is also an urgent need for standardised screening tests for immune disorders that could preclude implantation.

Investigation of a transient increase in omphalocele prevalence in a birth cohort of TRICARE beneficiaries.

BACKGROUND: The Department of Defense Birth and Infant Health Research (BIHR) program leverages medical encounter data to conduct birth defect surveillance among infants born to military families. Omphalocele is a major abdominal wall defect with an annual prevalence of ~2 per 10,000 births in BIHR data, but an unexpected increase was observed during 2017-2019, reaching 6.4 per 10,000 births in 2018. To investigate this transient increase in prevalence, this study aimed to validate the omphalocele case algorithm among infants born 2016-2021. METHODS: Omphalocele cases were identified by ICD-10 code Q79.2 (exomphalos) on one inpatient or two outpatient infant encounter records and validated using parental and infant electronic health records. Characteristics of true and false positive cases were assessed using bivariate analyses and compared over time. RESULTS: Of 638,905 live births from 2016 to 2021, 230 met the ICD-10 case definition for omphalocele; 138 (60.0%) cases were eligible for validation, of which 68 (49.3%) were true positives. The geometric mean time from birth to first ICD-10 omphalocele diagnosis was 1.1 (standard error [SE] 0.1) days for true positives and 11.9 (SE 3.1) days for false positives. Among the 70 false positives, 36 (51.4%) were cases of confirmed umbilical hernia; rates of umbilical hernia and delayed omphalocele diagnoses (>30 days after birth) were elevated among false positives during 2017-2019. CONCLUSIONS: Higher misuse of ICD-10 code Q79.2 during 2017-2019 likely influenced the associated increase in omphalocele prevalence. Timing of diagnosis should be considered for omphalocele case definitions using medical encounter data.

Mosaic embryo transfer versus additional IVF with PGT-A Cycle: a decision model comparing live birth rate and cost.

PURPOSE: To evaluate the relative live birth rate and net cost difference between mosaic embryo transfer and an additional cycle of IVF with PGT-A for patients whose only remaining embryos are non-euploid. METHODS: A decision analytic model was designed with model parameters varying based on discrete age cutoffs (<35, 35-37, 38-39, 40-42, 43-44, >44). Model inputs included probabilities of successful IVF, clinical pregnancy, and live birth as well as costs of IVF with PGT-A, embryo transfer, live birth, amniocentesis, and dilation and curettage. All costs were modeled from the healthcare system perspective and adjusted for inflation to 2023 $USD. Model outcomes were sub-stratified by degree and type of mosaicism. RESULTS: For patients younger than 43, an additional cycle of IVF with PGT-A resulted in a higher relative live birth rate (<35, +20%; 35-37, +15%; 38-39, +17%; 40-42, +6%; average, +14.5%) compared to mosaic embryo transfer with an average additional cost of $16,633. For patients older than 42, mosaic embryo transfer resulted in a higher live birth rate (43-44, +5%; >44, +3%; average, +4%) while on average costing $9572 less than an additional cycle of IVF with PGT-A. CONCLUSION: Mosaic embryo transfers are a superior alternative to an additional cycle of IVF with PGT-A for patients older than 42 whose only remaining embryos are non-euploid. Mosaic embryo transfers also should be considered for patients younger than 42 who are unable to pursue additional autologous IVF cycles. Counseling and care should be personalized to individual patients and embryos.

Correlation of self-reported racial background to euploidy status and live birth rates in assisted reproductive technology cycles.

PURPOSE: To determine whether the embryonic euploidy rate and live birth outcomes following single, euploid embryo transfer (SEET) differ among women of self-reported racial and ethnic backgrounds. METHODS: This retrospective cohort study included all infertile patients of different self-reported racial backgrounds who underwent In vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) and an autologous single euploid embryo transfer (SEET) from December 2015 to December 2019 at a single private and academic assisted reproduction technology center. Primary outcome measures included ploidy rates among different racial groups. Secondary outcomes included clinical pregnancy, clinical pregnancy loss, and live birth rates. RESULTS: Five thousand five hundred sixty-two patients who underwent an IVF cycle with ICSI-PGT-A were included. A total of 24,491 blastocysts were analyzed. White participants had on average more euploid embryos and higher euploidy rates when compared to their counterparts (p ≤ 0.0001). However, after controlling for confounding factors, there was no association between race and the odds of having  a higher euploidy rate (aOR 1.31; 95% CI 0.63-2.17, p = 0.42). A total of 4949 patients underwent SEET. Pregnancy outcomes did not differ among patients of varying self-reported races. CONCLUSIONS: Euploidy rates and pregnancy outcomes were comparable among patients of different racial backgrounds who underwent a SEET.

Prevalence, trend, and associated risk factors for cleft lip with/without cleft palate: a national study on live births from 2016 to 2021.

BACKGROUNDS: Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors. METHODS AND MATERIALS: In this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling. RESULTS: The total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79-4.97), for both sexes, and 5.96 (5.82-6.10) for males, and 3.75 (3.64-3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01-1.13, p = 0.013), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33-1.60, p <  0.001), mothers with extreme obesity (OR = 1.32, 1.21-1.43, p <  0.001), mothers with grade II obesity (OR = 1.32, 1.23-1.42, p <  0.001), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04-1.31, p = 0.009), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71-2.25, p <  0.001), and mothers who used assisted reproductive technology (OR = 1.40, 1.18-1.66, p <  0.001). CONCLUSIONS: Our findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.

Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis: A Systematic Review and Meta-Analysis.

Importance: Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue. Objective: To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation. Data Sources: In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. Study Selection: Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes. Data Extraction and Synthesis: Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted. Main Outcomes and Measures: The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI. Results: This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97). Conclusions and Relevance: This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.

The effect of female body mass index on cumulative live birth rate in women undergoing in vitro fertilization according to age.

The aim of this study was to explore the impact of female body mass index (BMI) on cumulative live birth rates (CLBR) in patients treated with in vitro fertilization (IVF) and embryo transfer. A total of 2377 patients who visited the Reproductive Medical Center, Luoyang Maternal and Child Health Hospital from January 2015 to December 2021. The patients underwent the first IVF cycles. According to female BMI, patients were divided into 3 groups, group A: BMI ≤ 18.5 kg/m2 (underweight), group B: BMI: 18.5 to 24.0 kg/m2 (normal), group C: BMI ≥ 24.0 kg/m2 (overweight/obesity). Patient basic parameters and clinical outcomes were compared among these 3 groups. Multivariate logistic regression analysis was used to explore the impact of BMI on CLBR. In all treatment cycles, patients' basic parameters were significantly different among 3 BMI groups. Age of underweight patient was younger than patients in the other 2 groups (28.45 ±â€…5.32 vs 29.89 ±â€…5.00 vs 30.74 ±â€…5.40; P = .000). In addition, number of oocytes retrieved was also significantly higher in group A (11.25 ±â€…5.97 vs 11.07 ±â€…5.49 vs 10.52 ±â€…5.02; P = .000). CLBR in these 3 groups were 66.40%, 65.98%, and 59.14%, respectively. In logistic analysis, overweight/obesity was associated with CLBR in young patients (aOR = 0.822, 95% CI: 0.817-0.957, P = .000). However, in the cycles of older patients, the effect of overweight/obesity on the CLBR was not significant (aOR = 0.986, 95% CI: 0.903-1.027, P > .05). Overweight/obesity is a predictor for CLBR in younger patients (<35 years old), but not in advanced age patients undergoing their first IVF/intracytoplasmic sperm injection treatment cycles.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

BACKGROUND: During a stimulated cycle of in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. A normal response to stimulation (e.g. retrieval of 5 to 15 oocytes) is considered desirable. Generally, the number of eggs retrieved is associated with the dose of FSH. Both hyper-response and poor response are associated with an increased chance of cycle cancellation. In hyper-response, this is due to increased risk of ovarian hyperstimulation syndrome (OHSS), while poor response cycles are cancelled because the quantity and quality of oocytes is expected to be low. Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response. Traditionally, this meant women's age, but increasingly, clinicians use various ovarian reserve tests (ORTs). These include basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose improves clinical outcomes. This review updates the 2018 version. OBJECTIVES: To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, and two trial registers in February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared (a) different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal, or high responders based on AMH, AFC, and/or bFSH) or (b) an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. MAIN RESULTS: We included 26 studies, involving 8520 women (6 new studies added to 20 studies included in the previous version). We treated RCTs with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence certainty ranged from very low to low, with the main limitations being imprecision and risk of bias associated with lack of blinding. Direct dose comparisons according to predicted response in women Due to differences in dose comparisons, caution is required when interpreting the RCTs in predicted low responders. All evidence was low or very low certainty. Effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy. Similarly, in predicted normal responders (10 studies, 4 comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units (IU): odds ratio (OR) 0.88, 95% confidence interval (CI) 0.57 to 1.36; I2 = 0%; 2 studies, 522 women) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the OHSS outcome to enable inferences. In predicted high responders, lower doses may or may not affect live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; 1 study, 521 women), severe OHSS, and clinical pregnancy. It is also unclear whether lower doses reduce moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; 1 study, 521 participants). ORT-algorithm studies Eight trials compared an ORT-based algorithm to a non-ORT control group. It is unclear whether live birth/ongoing pregnancy and clinical pregnancy are increased using an ORT-based algorithm (live birth/ongoing pregnancy: OR 1.12, 95% CI 0.98 to 1.29; I2 = 30%; 7 studies, 4400 women; clinical pregnancy: OR 1.04, 95% CI 0.91 to 1.18; I2 = 18%; 7 studies, 4400 women; low-certainty evidence). However, ORT algorithms may reduce moderate or severe OHSS (Peto OR 0.60, 95% CI 0.42 to 0.84; I2 = 0%; 7 studies, 4400 women; low-certainty evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.74, 95% CI 0.42 to 1.28; I2 = 0%; 5 studies, 2724 women; low-certainty evidence). Our findings suggest that if the chance of live birth with a standard starting dose is 25%, the chance with ORT-based dosing would be between 25% and 31%. If the chance of moderate or severe OHSS with a standard starting dose is 5%, the chance with ORT-based dosing would be between 2% and 5%. These results should be treated cautiously due to heterogeneity in the algorithms: some algorithms appear to be more effective than others. AUTHORS' CONCLUSIONS: We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT) affected live birth/ongoing pregnancy rates, but we could not rule out differences, due to sample size limitations. Low-certainty evidence suggests that it is unclear if ORT-based individualisation leads to an increase in live birth/ongoing pregnancy rates compared to a policy of giving all women 150 IU. The confidence interval is consistent with an increase of up to around six percentage points with ORT-based dosing (e.g. from 25% to 31%) or a very small decrease (< 1%). A difference of this magnitude could be important to many women. It is unclear if this is driven by improved outcomes in a particular subgroup. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU. However, the size of the effect is also unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates. It is likely that different ORT algorithms differ in their effectiveness. Current evidence does not provide a clear justification for adjusting the dose of 150 IU in poor or normal responders, especially as increased dose is associated with greater total FSH dose and cost. It is unclear whether a decreased dose in predicted high responders reduces OHSS, although this would appear to be the most likely explanation for the results.

Systematic review analyzing significance of endometrial cavity fluid during assisted reproductive techniques.

OBJECTIVE: The objective of our study is to estimate the prevalence of endometrial cavity fluid (ECF) in Assisted Reproductive Techniques (ART) cycles and analyze its effects on pregnancy outcome in such cycles. DATA SOURCES: PubMed, Cochrane Central, Scopus, and clinicaltrials.gov were searched for articles. The reference lists of relevant publications were explored for other studies. STUDY ELIGIBILITY CRITERIA: Studies that had assessed the pregnancy outcome in ART cycles and had commented on ECF accumulation were included. Pregnancy outcomes were assessed in all ART cycles where ECF was observed and were compared to the non-ECF cycles. RESULTS: A total of nine studies were included in the meta-analysis for a total of 28,210 cycles. Pooled analysis of the prevalence of ECF cycles out of total cycles in females undergoing ART using a fixed effect model showed that it was 14% (95% CI is 13% to 14%; I2 = 99%, p = < 0.01). The random effect model prevalence of ECF cycles was around 7% (95% CI: 4% to 10%). There was a statistically significant (25%) decrease in pregnancy rates per cycle transfer in the ECF cycle versus the non-ECF cycle group during ART [OR = 0.75, 95% CI = 0.67-0.84), p < 0.001; moderate quality evidence]. When ECF size was compared, there was a statistically significant increase in pregnancy rates if ECF size was less than 3.5 mm versus greater than or equal to 3.5 mm [OR = 13.67, 95% CI = 1.43-130.40), p = 0.02; high quality evidence]. Sub-group analysis revealed that the ECF present at the time of embryo transfer significantly decreased the pregnancy rates by 26% as compared to the group where the ECF was not present at the time of embryo transfer [OR = 0.74, 95% CI = 0.65-0.85), p < 0.001]. CONCLUSIONS: This meta-analysis proposes that the presence of ECF significantly decreases the implantation and pregnancy rates of ART cycles, and even more so if its size is greater than 3.5 mm. Interventions to decrease ECF formation or treat it have enhanced the pregnancy outcome in ART cycles. PROSPERO REGISTRATION: Date: 17th September 2020; Number: CRD42020182262.

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.

Does SARS Cov-2 infection affect the IVF outcome - A systematic review and meta-analysis.

STUDY QUESTION: What is the effect of SARS Cov-2 on IVF outcome? SUMMARY ANSWER: Mild or asymptomatic Covid-19 infection does not appear to affect clinical or ongoing pregnancy rate after IVF. WHAT IS ALREADY KNOWN: Covid-19 has been shown to affect female and male fertility and reproductive function. Studies have shown variable results regarding impact of Covid-19 on IVF outcome with few reporting impaired ovarian reserve, oocyte and embryo quality, semen parameters, clinical pregnancy rate (CPR) and live birth rate (LBR) while others reported no effect on IVF outcome. STUDY DESIGN, SIZE, DURATION: An electronic database search of PubMed, EMBASE, SCOPUS, WHO Covid-19 database, Clinical trials.gov and Cochrane Central was performed for articles published in English language between 1st January 2020 and 15th October 2022 by two independent reviewers using predefined eligibility criteria We have included observational studies both prospective and retrospective, cohort studies, and case control studies and excluded narrative reviews, case studies, cost-effectiveness studies or diagnostic studies. Risk of bias was assessed using NOS and quality of evidence was graded by GRADE pro. PARTICIPANTS, SETTINGS, METHODS: Studies comparing women undergoing IVF and comparing Covid-19 affected with those unaffected by Covid-19 were included. Also, studies comparing immune group (infected or vaccinated) in the study group and unaffected as controls (historical controls, IVF cycles done prior to Covid-19 outbreak but matched with study group) were included. Those with no comparison group or published in language other than English language or duplicate studies were excluded. MAIN RESULTS AND ROLE OF CHANCE: We identified 5046 records and after full text screening of 82 studies, 12 studies were selected for final review. For the clinical pregnancy rate, there was no difference in the CPR in covid recovered or control patients (OR 0.90, 95 % CI = 0.67 to1.21; I2 = 29 %). Similarly, there was no significant effect on implantation rate (RR 0.92, 95 % CI = 0.68 to1.23; I2 = 31 %) and ongoing pregnancy rate (RR 0.96, 95 % CI = 0.79 to 1.15;I2 = 21 %). The mean number of the oocyte retrieved per patient was not significantly different in both the groups (mean difference 0.52, 95 % CI = -1.45 to 2.49; I2 = 75 %). The certainty of the evidence was low. LIMITATIONS: The meta-analysis is based on observational studies each involving small number of participants. Few studies reported outcomes as per patient while others reported as per cycle, for uniformity we have reported outcomes as per cycle. Sample size in most of studies was small. WIDER IMPLICATIONS OF FINDINGS: This systematic review has not shown any significant effect on the outcome of IVF cycles in patients post Covid-19 recovery compared to controls. But given the sample size, the findings should be considered with caution. REGISTRATION: The review protocol has been registered on PROSPERO (registration number CRD42022314515).

Conception and pregnancy among women with a live birth after breast cancer treatment: A survey study of young breast cancer survivors.

BACKGROUND: Breast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling. METHODS: In the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0-III BC who reported ≥1 postdiagnosis live birth were sent an investigator-developed survey. RESULTS: Of 119 eligible women, 94 (79%) completed the survey. Median age at diagnosis was 32 years (range, 17-40) and at first postdiagnosis delivery was 38 years (range, 29-47). Most had stage I or II (77%) and HR+ (78%) BC; 51% were nulligravida at diagnosis. After BC treatment, most (62%) conceived naturally, though 38% used assisted reproductive technology, 74% of whom first attempted natural conception for a median of 9 months (range, 2-48). Among women with a known inherited pathogenic variant (n = 20), two underwent preimplantation genetic testing. Of 59 women on endocrine therapy before pregnancy, 26% did not resume treatment. Hypertensive disorders of pregnancy (20%) was the most common obstetrical condition. Nine percent of newborns required neonatal intensive care unit admission and 9% had low birth weight. CONCLUSION: Among women with live births after BC treatment, most conceived naturally and having a history of BC did not appear to negatively impact pregnancy complications, though the high rate of hypertensive disorders of pregnancy warrants further investigation. The prolonged period of attempting natural conception for some survivors suggests the potential need for improved understanding and counseling surrounding family planning goals after BC.

Association of overweight and obesity with cumulative live birth rates according to women's age: A cohort study of 26 567 treatment cycles.

OBJECTIVE: To evaluate the effect of age on the association between maternal body mass index (BMI) and cumulative live birth rates (CLBRs) following in vitro fertilization treatment. METHOD: We retrospectively analyzed the data of 26 567 women undergoing in vitro fertilization/intracytoplasmic sperm injection from 2016 to 2019. We conducted multivariate regression analysis of the association between CLBRs and maternal BMI and age category. RESULTS: A total of 16 626 (62.58%) patients achieved a live birth. Women with obesity had significantly decreased CLBRs compared with women who had normal weight (odds ratio [OR] 0.73 [95% confidence interval (CI), 0.66-0.80]). The significant interaction between age and BMI suggested that the impact of BMI on CLBRs was moderated by women's age (P interaction <0.001). The association between obesity and CLBRs was inverse among women aged <30 years (OR, 0.63 [95% CI, 0.54-0.73]), 30 to 34 years (OR, 0.79 [95% CI, 0.67-0.93]), and 35 to 37 years (OR, 0.71 [95% CI, 0.52-0.98]); however, decreases in CLBRs with obesity were not observed in women aged 38 to 40 years (OR, 1.17 [95% CI, 0.70-1.94]) and ≥ 41 years (OR, 1.25 [95% CI, 0.53-2.96]). CONCLUSION: Maternal obesity was significantly associated with a lower likelihood of having a live birth, but the risk differed according to women's age. A higher BMI might have a less-pronounced detrimental effect with increasing age.