Association between ambient temperature exposure and pregnancy outcomes in participants undergoing IVF: a retrospective cohort study.

Day 2 embryo transfer (ET) and day 3 ET afford similar reproductive outcomes in the poor responder

Does ambient temperature exposure affect outcomes including clinical pregnancy and live birth in women undergoing IVF? Both extreme cold and hot ambient temperatures were significantly associated with adverse pregnancy outcomes of IVF cycles. Heat exposure has been linked to adverse pregnancy outcomes worldwide. However, the effect of ambient temperature on infertile women undergoing IVF treatment is unclear. A retrospective cohort study was conducted from a database of 3452 infertile women who underwent their first fresh or frozen embryo transfer in the Shanghai First Maternity and Infant Hospital from April 2016 to December 2020. Daily mean ambient temperature exposure for each patient was obtained based on their residential address. Temperature-stratified multiple logistic regression analysis was performed to investigate associations between temperature exposure and pregnancy outcomes after controlling for confounders. Vulnerable sub-groups were identified using forest plots. The clinical pregnancy rate and live birth rate were 45.7% and 37.1%, respectively. Regarding clinical pregnancy, a higher temperature during cold weather was significantly associated with a higher pregnancy rate in the period about 11 weeks before ovarian stimulation (adjusted odds ratio (aOR) = 1.102, 95% CI: 1.012-1.201). Regarding live birth, an increased temperature during cold weather was significantly related to a higher live birth rate in the period after confirmation of clinical pregnancy or biochemical pregnancy, with the aORs of 6.299 (95% CI: 3.949-10.047) or 10.486 (95% CI: 5.609-19.620), respectively. However, a higher temperature during hot weather was negatively associated with the live birth rate in the periods after confirmation of clinical pregnancy or biochemical pregnancy, with the aORs at 0.186 (95% CI: 0.121-0.285) or 0.302 (95% CI: 0.224-0.406), respectively. Moreover, the decline in live birth rates during cold and hot weather was accompanied by increased rates of early miscarriage (P < 0.05). Stratified analyses identified susceptibility characteristics among the participants. Climate monitoring data were used to represent individual temperature exposure levels according to the patient's residential address in the study. We were not able to obtain information of personal outdoor activity and use of indoor air conditioners in this retrospective study, which may affect actual temperature exposure. This study highlights that the ambient temperature exposure should be taken into account during IVF treatment and afterwards. There is a need to be alert to extremes in cold and hot ambient temperatures, especially during the period of follicle development and pregnancy. With this knowledge, clinicians can scientifically determine the timing of IVF treatment and reinforce patients' awareness of self-protection to minimize adverse pregnancy outcomes associated with extreme temperatures. This work was supported by a grant from the Clinical Research Plan of Shanghai Hospital Development Center [SHDC2020CR4080], a grant from the Science and Technology Commission of Shanghai Municipality [19411960500], and two grants from the National Natural Science Foundation of China [81871213, 81671468]. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva, and research grants from Merck KGaA, Ferring and Guerbet. The other authors have no conflict of interest to declare. N/A.

Oocyte retrieval versus conversion to intrauterine insemination in patients with poor response to gonadotropin therapy

Assisted reproductive technologies (ART) in Canada: 2004 results from the Canadian ART Register

What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. N/A.

Study question Does PGT-A, with or without an ERA, enhance pregnancy outcomes in patients with recurrent implantation failure undergoing IVF when compared to traditional morphological assessments? Summary answer PGT-A improves implantation, clinical pregnancy and live birth rates in RIF patients, while adding ERA does not significantly enhance outcomes. What is known already Recurrent implantation failure (RIF) is a major challenge in assisted reproductive technology (ART). Preimplantation genetic testing for aneuploidy (PGT-A) is commonly used to improve implantation by selecting euploid embryos. Endometrial receptivity assay (ERA) aims to optimise embryo transfer timing. However, the effectiveness of PGT-A and ERA in improving pregnancy outcome to RIF patients remains debated, with inconsistent findings across studies. Study design, size, duration Relevant studies published between January 2004 and January 2025 were systematically retrieved from PubMed, Embase, and the Cochrane Library databases. A total of 17 studies involving 7,240 cases met the inclusion criteria. Using a random-effects model, odds ratios (ORs) were calculated to assess key outcomes, including implantation, clinical pregnancy, ongoing pregnancy, live birth, and miscarriage rates. Participants/materials, setting, methods The analysis evaluated 7,240 recurrent implantation failure (RIF) cases across 17 studies. A random-effects model was employed to determine odds ratios (ORs) for implantation, clinical pregnancy, ongoing pregnancy, live births, and miscarriage rates. The study compared patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) only against those who received PGT-A along with the endometrial receptivity assay (ERA), in contrast to traditional morphological assessment of embryos alone. Main results and the role of chance The findings revealed that PGT-A significantly increased implantation rates (OR = 1.75, 95% CI: 1.27-2.40, p = 0.00), clinical pregnancy rates (OR = 1.67, 95% CI: 1.17-2.37, p = 0.00), and live birth rate rates (OR = 1.74, 95% CI: 1.30-2.31, p = 0.00). However, the procedure did not significantly decrease miscarriage rates (OR = 1.30, 95% CI: 0.79-2.14, p = 0.30). Furthermore, incorporating ERA into PGT-A protocols did not yield any significant improvement in outcomes for RIF patients (implantation rates OR = 3.94, 95% CI: 0.70-22.15, p = 0.12; clinical pregnancy rates OR = 2.42, 95% CI: 0.56-10.33, p = 0.23; live birth rates OR = 1.15, 95% CI: 0.35-3.77, p = 0.82; miscarriage rates OR = 0.34, 95% CI: 0.11-1.05, p = 0.06). Notable heterogeneity was present across studies (I2 = 45%-92%). Limitations, reasons for caution Significant heterogeneity across studies (I² = 45%-92%) may affect result reliability. Differences in study design, patient characteristics, and PGT-A/ERA protocols could introduce bias. Wider implications of the findings PGT-A improves implantation, clinical pregnancy, and live birth rates in RIF patients, supporting its role in embryo selection. However, adding ERA does not enhance outcomes, suggesting limited benefit in routine use. These findings may guide clinical decision-making in ART, emphasising the need for individualized treatment approaches. Trial registration number No

Recurrent IVF failure: other factors

ObjectiveTo investigate the factors that influence luteal phase short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH-antagonist (GnRH-ant) protocol on pregnancy outcome and quantify the influence. About the statistical analysis, it is not correct for the number of gravidities.MethodsInfertile patients (n = 4,631) with fresh in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer were divided into GnRH-a long protocol (n =3,104) and GnRH-ant (n =1,527) protocol groups and subgroups G1 (EMT ≤7mm), G2 (7 mm <EMT ≤10 mm), and G3 (EMT >10 mm) according to EMT on the trigger day. The data were analyzed.ResultsThe GnRH-ant and the GnRH-a long protocols had comparable clinical outcomes in the clinical pregnancy, live birth, and miscarriage rate after propensity score matching. In the medium endometrial thickness of 7–10 mm, the clinical pregnancy rate (61.81 vs 55.58%, P < 0.05) and miscarriage rate (19.43 vs 12.83%, P < 0.05) of the GnRH-ant regime were significantly higher than those of the GnRH-a regime. The EMT threshold for clinical pregnancy rate in the GnRH-ant group was 12 mm, with the maximal clinical pregnancy rate of less than 75% and the maximal live birth rate of 70%. In the GnRH-a long protocol, the optimal range of EMT was >10 mm for the clinical pregnancy rate and >9.5 mm for the live birth rate for favorable clinical outcomes, and the clinical pregnancy and live birth rates increased linearly with increase of EMT. In the GnRH-ant protocol, the EMT thresholds were 9–6 mm for the clinical pregnancy rate and 9.5–15.5 mm for the live birth rate.ConclusionsThe GnRH-ant protocol has better clinical pregnancy outcomes when the endometrial thickness is in the medium thickness range of 7–10 mm. The optimal threshold interval for better clinical pregnancy outcomes of the GnRH-ant protocol is significantly narrower than that of the GnRH-a protocol. When the endometrial thickness exceeds 12 mm, the clinical pregnancy rate and live birth rate of the GnRH-ant protocol show a significant downward trend, probably indicating some negative effects of GnRH-ant on the endometrial receptivity to cause a decrease of the clinical pregnancy rate and live birth rate if the endometrial thickness exceeds 12 mm.

PurposeTo investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT).MethodsThis study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method.ResultsThe NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model.ConclusionThis study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.

Clinical outcomes for various causes of infertility with natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes

PurposeTo compare pregnancy outcomes of four endometrial preparation methods prior to frozen embryo transfer (FET).MethodsA total of 3,030 programmed cycles were analyzed: 302 with natural cycle (NC), 131 with ovulation induction (OI), 1,078 with hormone replacement treatment (HRT), and 1,519 with GnRHa pretreatment (GnRHa + HRT). Primary outcomes investigated were positive human chorionic gonadotropin (hCG), chemical pregnancy, clinical pregnancy, abortion, and live birth. Additionally, the impact of age, body mass index (BMI), embryo number, high-quality embryo, and endometrial thickness on pregnancy outcomes were analyzed.ResultsThe positive hCG rates for NC, OI, HRT, and GnRHa + HRT groups were 63.4%, 62.6%, 68.3%, and 71.7%, respectively (P = 0.004). Clinical pregnancy rates were 50.4%, 54%, 57.5%, and 61.8%, respectively (P = 0.004). Live birth rates were 38.2%, 45%, 46.5%, and 50.9%, respectively (P = 0.007). No significant differences were found in abortion and chemical pregnancy rates among the four protocols. NC showed significantly higher positive hCG (p = 0.044), live birth (p = 0.005), and clinical pregnancy rates (p = 0.010) compared to other methods. Compared to HRT, GnRHa + HRT displayed significantly higher live birth (p = 0.027) and clinical pregnancy rates (p = 0.027). Multiple logistic regression showed that the number of embryos and high-quality embryos increased HCG positivity, clinical pregnancy, and live birth rates, while age reduced these rates. BMI increased the abortion rate, and endometrial thickness increased the live birth rate. Chemical pregnancy was unaffected by these factors.ConclusionNC offers improved outcomes compared to other methods. Additionally, specific factors such as embryo quality and embryo number significantly influence pregnancy outcomes.Clinical trial numberNot applicable.

A review of factors influencing the implantation of euploid blastocysts after in vitro fertilization

Maternal chronic hepatitis B virus infection does not affect pregnancy outcomes in infertile patients receiving first in vitro fertilization treatment

Is in vitro maturation (IVM) as successful as standard in vitro fertilization (IVF) for the treatment of patients with polycystic ovaries (PCO) in terms of fresh, frozen and cumulative pregnancy outcomes? There was no difference in clinical pregnancy rates in fresh or frozen embryo transfer (FET) cycles between the two treatment groups however, the IVM group showed a lower clinical pregnancy rate cumulatively. There was significantly fewer live births resulting from IVM treatment for both fresh and cumulative cycle outcomes however, there was no difference in live birth rates resulting from FETs between IVM and IVF treatment. IVM is well recognized as the only treatment option to eliminate completely the incidence of ovarian hyperstimulation syndrome. However, historically IVM has been less successful than standard IVF in terms of clinical pregnancy, implantation and live birth rates. This paper represents a retrospective case-control study. The study involved 121 participants who underwent 178 treatment cycles. Cycles were completed between March 2007 and December 2012. All fresh cycles and subsequent FET cycles were included in the analysis to calculate cumulative outcomes. All participants were prospectively diagnosed with PCO morphology or polycystic ovarian syndrome (PCOS) and underwent either IVM or standard IVF treatment. Their treatment outcomes were analysed with regard to embryological data, and the rate of biochemical pregnancy, clinical pregnancy and live birth, in addition maternal and neonatal outcomes were assessed. Fifty-six patients underwent 80 cycles of IVM treatment and 65 patients underwent 98 cycles of standard IVF treatment. For fresh cycles, the differences in the biochemical pregnancy, clinical pregnancy or miscarriage rates between the two treatment groups were not statistically significant. The IVM group showed significantly lower live birth rates in fresh cycles in comparison to standard IVF treatment (18.8 versus 31.0%, P = 0.021). For frozen embryo transfer (FET) cycles the differences in biochemical pregnancy, clinical pregnancy, live birth or miscarriage rates between the two treatments groups were not statistically significant. The cumulative biochemical pregnancy (67.5 versus 83.7%, P = 0.018), clinical pregnancy (51.3 versus 65.3%, P = 0.021) and live birth rates (41.3 versus 55.1%, P = 0.005) were significantly lower in the IVM group in comparison to the standard IVF treatment group. There was no overall difference in the cumulative miscarriage rates between the two treatment groups. There was no difference between treatment methods with regard to the neonatal outcomes, and the IVM group had a significantly lower rate of ovarian hyperstimulation syndrome (0 versus 7.1%, P < 0.001). This was an observational study and further randomized clinical trials are required to clarify the difference in outcomes between standard IVF and IVM for patients with PCO/PCOS. This is the first study to compare IVM with standard IVF in PCO/PCOS patients using blastocyst development and single embryo transfer. Furthermore, it is the first study to show the results of fresh, frozen and cumulative treatment cycle outcomes between the two groups. Our results show similar success rates to those reported from other groups, particularly in relation to the incidence of miscarriage in fresh IVM cycles and improved success from FET cycles. Maternal and neonatal outcomes are consistent with the limited literature available. The study was supported by the Women's and Infant's Research Foundation of Western Australia. Professor Hart is Medical Director of Fertility Specialists of Western Australia (FSWA) and a shareholder Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. T.H. is a consultant with FSWA and a shareholder in Western IVF. She has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. The other authors have no competing interests.

The aim of this study was to investigate the effect of the endometrial thickness (EMT) measured on embryo transfer day on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) in fresh and frozen-thawed embryo transfer cycles. This prospective cohort study consisted of 160 patients, 80 frozen-thawed and 80 fresh cycles. Endometrial thickness was measured on the day of embryo transfer for fresh and frozen cycles. In addition to the endometrial thickness, the endometrial appearances of the patients in both groups were also recorded. Those without trilaminar appearance were excluded from the study. Both groups were classified according to the EMT values measured on the day of the transfer. The number of groups was calculated considering 1 mm intervals of EMT, and a total of 8 groups were formed. The initial group started with <6 mm, while the final group was >12 mm. The relationship between endometrial thickness, clinical pregnancy, live birth and miscarriage rates was analyzed using multivariable regression analysis. A significant correlation was observed between endometrial thickness values, clinical pregnancy rates, live birth rates in the analyses performed after adjusting for age, infertility duration, body mass index, number of MII oocytes, number and quality of embryos transferred. Based on univariate analysis, each 1 mm increase in EMT resulted in a significant increase in CPR (OR=1.08, 95% CI: 1.07-1.09, p<0.01). Similarly, the increase in EMT led to a significant increase in LBR (OR=1.12, 95% CI: 1.10-1.14, p<0.01). Although the relationship between miscarriage rates and EMT is not as clear as LBR and CPR, the increase in EMT led to a significant reduction in MR (OR=1.05, 95% CI: 1.03-1.05, p=0.03). The lowest CPR was detected at EMT <6 mm, while the EMT value with the highest CPR was 11-12 mm in both groups. Likewise, in both groups, the lowest LBR was detected at EMT <6 mm, while the EMT value with the highest LBR was 11-12 mm. Although MR showed a fluctuating course according to EMT values, it reached its highest rate at EMT <6 mm (100%). In EMT 11-12 mm, MR reached its lowest level (12.5%). If EMT >12 mm, an increase in MR rates was observed again (33.3%). Clinical pregnancy and live birth rates remain optimal if the endometrial thickness is between 11-12 mm in both fresh and frozen-thawed cycles. A fluctuating course is observed between EMT values and miscarriage rates.