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Study Question: Does ambient temperature exposure affect outcomes including clinical pregnancy and live birth in women undergoing IVF?, Summary Answer: Both extreme cold and hot ambient temperatures were significantly associated with adverse pregnancy outcomes of IVF cycles., What Is Known Already: Heat exposure has been linked to adverse pregnancy outcomes worldwide. However, the effect of ambient temperature on infertile women undergoing IVF treatment is unclear., Study Design, Size, Duration: 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., Participants/materials, Setting, Methods: 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., Main Results and the Role of Chance: 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., Limitations, Reasons for Caution: 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., Wider Implications of the Findings: 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., Study Funding/competing Interest(s): 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., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In assisted reproductive technology treatment, diminished ovarian reserve (DOR) is a condition of utmost clinical and scientific relevance because of its negative influence on patient outcomes. The current methods of infertility treatment may be unsuitable for many women with DOR, which support the need for development of additional approaches to achieve fertility restoration. Various techniques have been tried to improve the quality and increase the quantity of oocytes in DOR patients, including mitochondrial transfer, activation of primordial follicles, in vitro culture of follicles, and regeneration of oocytes from various stem cells. Herein, we review the science behind these experimental reproductive technologies and their potential use to date in clinical studies for infertility treatment in women with DOR., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although it is well appreciated that ovarian stimulation protocols for in vitro fertilization (IVF) alter endometrial receptivity, the precise cellular mechanisms are not known. To gain insights into potential mechanisms by which different ovarian stimulation protocols alter the endometrium, we compared histologic and gene expression profiles of endometrium from women undergoing conventional ovarian stimulation for IVF (C-IVF) with those undergoing minimal stimulation with clomiphene citrate (MS-IVF). Sixteen women undergoing MS-IVF (n = 8) or C-IVF (n = 8) were recruited for endometrial biopsy at the time of oocyte retrieval. Endometrial glands were large, tortuous, and secretory with C-IVF but small and undifferentiated with MS-IVF. Whereas RNA sequencing did not reveal changes in estrogen receptor or its co-regulators or classic proliferation associated genes in MS-IVF, together with immunohistochemistry, Wnt signaling was disrupted in endometrium from MS-IVF cycles with significant upregulation of Wnt inhibitors. Secreted frizzled-related protein 1 (sFRP1) was increased fourfold (p < 0.01), and sFRP4 was upregulated sixfold (p < 0.01) relative to C-IVF. Further these proteins were localized to subepithelial endometrial stroma. These data indicate that MS-IVF protocols with CC do not seem to impact endometrial estrogen signaling as much as would be expected from the reported antiestrogenic properties of CC. Rather, the findings of this study highlight Wnt signaling as a major factor for endometrial development during IVF cycles.

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To examine codified state policies related to infertility and assess their implications for cancer patients. Lack of insurance is often identified as a barrier to use of fertility preservation (FP) services., Design: None., Setting: A keyword search was developed to identify statutes and administrative regulations of insurance coverage for FP in the United States., Patient(s): N/A., Intervention(s): N/A., Main Outcome Measure(s): Laws addressing the general population but pertaining to FP were compiled using Lexis-Nexis. Data were analyzed by reviewing the "plain meaning" of the text, legislative/administrative history, and annotated case law. Legal reasoning and common rules of statutory construction and legislative interpretation were used., Result(s): Fifteen states (29.4%) had laws relating to insurance coverage for infertility or in vitro fertilization (IVF) procedures and two states (CA and IL) specifically excluded IVF from a mandatory offer of coverage. No state laws or regulations addressed insurance coverage for FP methods specific to cancer patients., Conclusion(s): There is an argument for policies that require coverage for FP for cancer survivors before treatment., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether women with hydrosalpinx would have diminished endometrial HOXA10 expression and whether salpingectomy would reverse HOXA10 suppression. The homeobox gene HOXA10 is a transcription factor that is necessary for embryo implantation; its expression in human endometrium correlates with receptivity and implantation. Increased endometrial HOXA10 expression may be one mechanism by which salpingectomy results in increased implantation rates in IVF., Design: Prospective clinical trial., Setting: Academic medical center., Patient(s): Women with unilateral or bilateral hydrosalpinx., Intervention(s): Expression of HOXA10 was examined prospectively during the midluteal phase in endometrium obtained from infertile women (n = 9) with hydrosalpinges before and after salpingectomy, as well as from fertile controls (n = 6). Quantitative HOXA10 mRNA expression was determined by real-time reverse-transcription polymerase chain reaction, and HOXA10 protein expression was determined by immunohistochemistry., Main Outcome Measure(s): Expression of HOXA10 mRNA and protein., Result(s): Expression of HOXA10 mRNA was significantly lower in infertile women with hydrosalpinges, compared with the case of fertile controls. Salpingectomy resulted in a statistically significant, 15-fold increase in endometrial HOXA10 expression. Immunohistochemical analysis confirmed the quantitative real-time reverse-transcription polymerase chain reaction findings. Increased HOXA10 expression was evident in both glandular epithelial cells and endometrial stroma., Conclusion(s): HOXA10 is necessary for implantation. Here, we demonstrate decreased HOXA10 expression in response to hydrosalpinx fluid as a potential molecular mechanism for diminished implantation rates. Salpingectomy restores endometrial HOXA10 expression. This may be one mechanism by which salpingectomy results in augmented implantation rates in IVF.

Background: The presence of hydrosalpinges is associated with lower implantation and pregnancy rates in women undergoing IVF-embryo transfer, while salpingectomy improves these parameters. Although the mechanism by which hydrosalpinges affects fertility is not entirely understood, an adverse effect on endometrial receptivity has been postulated. In this study, we hypothesized that the adverse effects of hydrosalpinges on fertility may be in part mediated by inappropriate endometrial expression of leukaemia inhibitory factor (LIF), a cytokine implicated in implantation., Methods: In order to test our hypothesis, we prospectively examined the expression of LIF during the window of implantation in the endometrium of infertile women (n = 10) with hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 10) by Western blotting and immunohistochemistry., Results: LIF expression was significantly lower in infertile women with hydrosalpinges compared with fertile controls (P < 0.05). Salpingectomy resulted in an increase in LIF expression in eight out of 10 women with hydrosalpinges. LIF levels were increased by 231 +/-49% (mean +/- SEM) following salpingectomy. Immunohistochemical analysis confirmed the Western blot findings. The increased LIF immunoreactivity was predominantly localized to luminal and glandular epithelial cells., Conclusions: Our findings suggest that observed benefit from salpingectomy in infertile women with hydrosalpinges may be in part mediated by the up-regulation of endometrial LIF expression.

Purpose of Review: Various methods have been proposed and are currently used in the assessment of ovarian reserve in order to predict the outcome in assisted reproduction. This review focuses on the current information regarding the ovarian reserve markers and tests, an active area of research., Recent Findings: Female age alone is a rough parameter for assessing ovarian reserve. The basal follicle stimulating hormone level is not adequately sensitive to predict poor outcome and the same is true for other basal parameters, including basal estradiol, the follicle stimulating hormone/luteinizing hormone ratio, and inhibin-B levels. The clomiphene citrate challenge test has a low sensitivity but this sensitivity is greater than that of basal follicle stimulating hormone. The value of other hormonal dynamic tests remains to be determined. Among the ultrasound markers the total antral follicle count seems to be promising. Ovarian biopsy in this assessment is controversial. History of poor response to ovarian stimulation is a strong indicator for declining ovarian function., Summary: There is currently no clinically useful predictive test sufficiently accurate and distinct in time from controlled ovarian stimulation to assess ovarian reserve accurately. Further research is warranted to validate the ovarian reserve tests in the general population and in populations with different causes of infertility.

Objective: To compare the efficacy of intracytoplasmic sperm injection and IVF in women with a tuboperitoneal factor as their sole cause of infertility., Design: Prospective, randomized study., Setting: Hacettepe University Assisted Reproduction Unit, Ankara, Turkey., Patient(s): Seventy-six consecutively seen patients with tuboperitoneal factor infertility were randomized on an alternate basis to undergo either intracytoplasmic sperm injection (38 patients and cycles) or IVF (38 patients and cycles)., Intervention(s): Intracytoplasmic sperm injection and IVF., Main Outcome Measure(s): Fertilization, implantation, and clinical pregnancy rates., Result(s): A comparable number of oocytes and embryos were obtained with intracytoplasmic sperm injection and IVF. The two-pronuclei fertilization rates per metaphase II oocyte or mature cumulus-oocyte complex were similar in the two groups. The numbers of total and grade I embryos transferred also were similar. Comparisons of intracytoplasmic sperm injection and IVF did not reveal any statistically significant differences in individual implantation rates (38.75% +/- 24.46% and 34.58% +/- 16.97%, respectively) clinical pregnancy rates per cycle (21.05% and 21.05%, respectively), or take-home infant rates (18.42% and 15.79%, respectively). The type of procedure performed was not a significant predictor of clinical pregnancy., Conclusion(s): When a decision is made to proceed with an assisted reproductive technique in patients with a tubal factor as their sole cause of infertility, IVF should be the initial treatment of choice.

Objective: To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation., Design: Prospective, randomized trial., Setting: University-based infertility clinic., Patient(s): Fifty-one women., Intervention(s): Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken., Main Outcome Measure(s): Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate., Result(s): Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered., Conclusion(s): Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol.