Inverse association of prepregnancy systolic blood pressure and live birth rate in normotensive women undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To explore whether maternal baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) affect pregnancy outcomes particularly in normotensive women (SBP, 90-139 mm Hg; DBP, 60-89 mm Hg) and hypertensive women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective cohort study. SETTING: Maximum care hospital for reproductive medicine. PATIENT(S): This study included 73,462 patients who underwent IVF/ICSI at the Reproductive and Genetic Hospital of CITIC-Xiangya between January 1, 2016, and November 30, 2020, selected on the basis of pre-established criteria. Analysis was limited to the first transfer cycle of the first stimulation cycle. INTERVENTION: Baseline SBP and DBP. MAIN OUTCOME MEASURE(S): The primary outcome focused on the live birth rate (LBR), with the secondary outcomes including clinical pregnancy rate, ectopic pregnancy rate, first-trimester miscarriage rate, second- or third-trimester fetal loss, and delivery/neonatal/maternal outcomes. Analytic methods included Poisson regression, linear regression, linear mixed-effect model, and restricted cubic spline analysis as appropriate. RESULT(S): For normotensive women, a 10-mm Hg increase in SBP was associated with an adjusted relative risk of 0.988 (95% confidence interval, 0.981-0.995) for live birth likelihood. However, DBP was not significantly associated with LBR after adjustments. The secondary outcomes indicated that increases in SBP and DBP were associated with higher risks of first-trimester miscarriage, gestational diabetes mellitus, and gestational hypertension in the normotensive subset. Sensitivity analyses confirmed these associations between SBP/DBP and LBR, consistent with the main findings even under stricter guidelines and after adjusting for multiple confounders. Subgroup analyses showed variation in the impact of blood pressure on LBR across different demographics and conditions. Consistent with earlier studies on blood pressure and birth outcomes, we found a 10-mm Hg increase in SBP was associated with a 5.4% (adjusted relative risk per 10 mm Hg, 0.946; 95% confidence interval, 0.907-0.986) reduction in LBR in the hypertensive subgroup. CONCLUSION(S): Systolic blood pressure impacted LBR outcomes in normotensive women who underwent IVF/ICSI, which suggests the need for reconsidering blood pressure management guidelines for reproductive-age women, focusing on reproductive health in addition to cardiovascular risk.

Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis.

STUDY QUESTION: Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer? SUMMARY ANSWER: Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. WHAT IS KNOWN ALREADY: Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer. STUDY DESIGN SIZE DURATION: We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'. PARTICIPANTS/MATERIALS SETTING METHODS: We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies. MAIN RESULTS AND THE ROLE OF CHANCE: This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5-15%) and delivery rates per cycle of 23% (17-30%), 18% (11-26%), and 5% (1-9%) for ICSI, IVF, and IUI, respectively. LIMITATIONS REASONS FOR CAUTION: As with all meta-analyses, some limitations should be considered. The first limitation of our study is that the data span 36 years. During this time, the World Health Organization has revised its sperm analysis standards, and other important changes have been made. There is also a limitation in that the outcome does not analyze the correlation between the type of cancer and sperm quality. Many of the earlier studies were limited by small sample sizes and a lack of control groups. Furthermore, almost all studies did not consider the severity of the disease, which could potentially have a substantial impact on the results. Consequently, further research should evaluate the effect of the type of cancer and, in particular, the severity of the condition on sperm quality in order to draw more precise conclusions. Similarly, it is inappropriate that most studies failed to differentiate between patients with different types of tumors and instead drew generalized conclusions that are presumed to apply to all patients with cancer. In the present analysis, we did not have in-depth information on patients' disease, and although extensive efforts were made to conduct a thorough systematic review and meta-analysis of the outcomes for patients with various types of tumors, the results must be acknowledged as being subject to bias. However, the use of average results obtained in each study, without the patient-level data, might also represent a source of bias. WIDER IMPLICATIONS OF THE FINDINGS: Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. The observed utilization rate of frozen sperm at 9% may underestimate the actual usage, as the short follow-up period is inadequate for obtaining comprehensive data on the use of frozen sperm in young cancer survivors. ART plays an important role in fertility preservation and the achievement of pregnancy, with this meta-analysis showing that ICSI delivers better clinical outcomes than IVF or IUI in patients with cancer undergoing fertility preservation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (grant no. 82001634, 81960550), and the China Postdoctoral Science Foundation (2019M661521). There are no competing interests to declare. REGISTRATION NUMBER: CRID 42022314460.

Effect of re-cryopreservation on pregnancy and neonatal outcomes: Analysis using propensity score matching.

OBJECTIVE: To comprehensively assess the effect of re-cryopreservation procedure on pregnancy and neonatal outcomes by using propensity matching (PSM) analysis. METHODS: The patients were divided into two groups according to the times of embryo cryopreservation: the cryopreservation group (n = 8034) and the re-cryopreservation group (n = 66). To optimize the precision of the present study, we used PSM to adjust the different baseline characteristics between the two groups, including maternal age, the number of good-quality embryos transferred and endometrial preparation protocols. The primary outcome was live-birth rate. The secondary outcomes were biochemical pregnancy rate, clinical pregnancy rate, and miscarriage rate. RESULTS: We found that the rates of biochemical pregnancy and clinical pregnancy were comparable between the two groups, whereas miscarriage rate was increased, resulting in significantly reduced live-birth rate in the re-cryopreservation group. No differences were observed in terms of neonatal outcomes, including cesarean section, birth weight, and malformation as well as pregnancy complications. Moreover, multivariable analysis demonstrated that re-cryopreservation was an independent risk factor for live-birth rate. CONCLUSION: The present study demonstrated the adverse effect of re-cryopreservation on pregnancy outcomes, providing valuable information for clinical decision making and patient counseling.

Improved pregnancy rate and sex ratio in fresh/frozen in vivo derived embryo transfer of Hanwoo (Bos taurus coreanae) cows.

This study aimed to assess the effects of embryonic developmental stage, quality grade, and fresh or frozen/thawed conditions on the pregnancy rate and sex ratio of live offspring in Hanwoo (Bos taurus coreanae) cows. The quality and developmental stage of in vivo-derived (IVD) transferred embryos were evaluated using the standard criteria of the International Embryo Technology Society. The recipient cows were synchronized using conventional (estradiol benzoate and progesterone) protocols before embryo transfer. Embryos were transferred to 297 cows, and pregnancy was monitored for 60-70 days after embryo transfer. The pregnancy rates of fresh and frozen/thawed embryos were 56.90% and 52.49%, respectively. Pregnancy rates varied according to embryo quality (56.18% for grade 1 vs. 36.67% for grade 2). Pregnancy rates also varied by developmental stage and cryopreservation (67.86% vs. 63.49% for stage 4-1, 64.00% vs. 54.72% for 5-1, and 50.00% vs. 47.83% for 6-1, in fresh embryos vs. frozen/thawed embryos, respectively). For stage 7-1, the pregnancy rates were 72.73% for fresh embryos and 20.00% for frozen/thawed embryos. In 66 fresh embryos, the sex ratio of live offspring was 5:5, whereas it was 4(female):6(male) for frozen/thawed embryos among the 95 frozen/thawed embryos. The miscarriage rate was approximately 3% higher for frozen/thawed embryos than for fresh embryos (18.1% for fresh vs. 21.1% for frozen). Seasonal fertility rates were 33.3% in spring, 55.67% in summer, 52.8% in autumn, 60.0% in winter. The following male-to-female ratios were observed in different seasons: 6.7:3.3 in spring, 4.0:6.0 in summer, 5.5:4.5 in autumn, and 3.3:6.7 in winter. The current data revealed no significant differences in pregnancy rates between fresh and frozen/thawed IVD embryos. However, there was a lower pregnancy rate with advanced-stage frozen/thawed embryos (stage 7-1). The current study provides comprehensive results for the better optimization of embryo transfer in Hanwoo cattle to obtain the desired fertility rate, pregnancy rate, and sex ratio of calves. These results provide important insights into the factors that influence the viability and success of IVD embryo transfer in Hanwoo cows and may have practical applications for improving breeding programs and reducing production costs.

The natural cycle protocol of endometrial preparation for frozen embryo transfer decreases the miscarriage rate in women with recurrent pregnancy loss.

OBJECTIVE: To investigate whether different endometrial preparation methods lead to different results. DESIGN: Retrospective cohort study. PATIENTS: Women with recurrent pregnancy loss undergoing frozen embryo transfer (FET). INTERVENTIONS: Natural cycle (NC) protocol (n = 111) with no drug or human chorionic gonadotropin (HCG) used for endometrial preparation, vs. the hormone replacement therapy (HRT) protocol (n = 797) with estrogen or gonadotropin releasing hormone agonist (GnRH-a) plus estrogen used for endometrial preparation. MAIN OUTCOME MEASURES: Miscarriage rate and live birth rate (LBR). RESULTS: Compared to women in the HRT protocol, women undergoing NCs had fewer previous FET cycles, lower antral follicle counts (AFCs), fewer oocytes retrieved and a thicker endometrium on the day of progesterone administration. Women in the HRT group had a higher miscarriage rate (29.4% vs. 17.2%) and a lower LBR (37% vs. 46.9%) than the rates of women in the NC group. Univariate analysis showed that female age also had a negative association with the miscarriage rate. Logistic regression indicated that endometrial preparation using the NC protocol was linked to a decreased likelihood of miscarriage. CONCLUSIONS: The NC protocol decreased the miscarriage rate and increased the LBR for patients with recurrent pregnancy loss compared with the HRT protocol.

Does the decrease in E2 levels between the trigger of ovulation and embryo transfer affect the reproductive outcome in IVF-ICSI cycles?

Objective: This study aimed to evaluate the effect of the rate of decline in serum estradiol (E2) levels between hCG injection and the day of embryo transfer (ET) on the success of assisted reproductive technology (ART) in women with infertility of different etiologies. Materials and Methods: Women 20-45 years of age who underwent a standard GnRH antagonist or long agonist protocol and fresh ET during day 3 of their first ART cycle were included. Group 1 was diagnosed with low ovarian reserve, group 2 comprised high ovarian responders, and group 3 consisted of normal responders. Both groups were divided into four subgroups according to the decrease in E2 levels between the day of hCG injection and the day of ET. Subgroup A patients had a decrease of <20%, subgroup B a decrease of 20-40%, subgroup C a decrease of 41-60%, and subgroup D a decrease >60%. The primary outcome measure was the effect of an E2 decline, based on the measurement of E2 on the day of hCG administration and day of ET, on the implantation rate. The secondary outcome was the change in E2 values in these three groups. Results: The study was conducted on 1.928 women. Of these, 639 were poor responders (group 1), 502 were high responders (group 2), and 787 women had a normal ovarian response (group 3). Patients with a 60% decrease in their E2 levels on the ET day after hCG had a lower live birth rate (LBR) and higher miscarriage rate (MCR), except normoresponders, in whom a similar decline was significant only with respect to MCR. Conclusion: We indicate that high ovarian responders who underwent fresh ET cycles with a 60% decrease in their E2 levels on the ET day after human chorionic gonadotropin had lower LBRs and higher miscarriage. However, in normoresponder women, this decline was only significant in miscarriage.

Higher miscarriage rate in subfertile women with endometriosis receiving unbiopsied frozen-warmed single blastocyst transfers.

Background: Assisted reproductive technology treatment is recommended to overcome endometriosis-associated infertility but current evidence is controversial. Endometriosis is associated with lower antral follicle count (AFC) and oocyte yield but similar clinical outcomes compared to controls. Unaffected ovarian stimulation response and embryological outcomes but lower clinical pregnancy and live birth rates and higher miscarriage rates have been reported, implying direct impact on endometrial receptivity. With evidence emerging on the benefit of frozen-warmed and blastocyst stage transfer, we investigated ART outcomes in endometriosis using homogeneous case-control groups. Methods: This is a retrospective observational case-control study including n = 66 frozen-warmed unbiopsied single blastocyst transfers of patients with endometriosis and n = 96 of women exhibiting idiopathic sterility. All frozen-warmed transfers followed artificial endometrial preparation. Results: In control women, the mean number of oocytes recovered at oocyte pick up was higher compared to women with endometriosis (15.3 ± 7.1 vs. 12.7 ± 5.2, p = 0.025) but oocyte maturation index (mature oocytes/total oocytes at oocyte pick up) was significantly higher for endometriosis (48.2% vs. 34.0%, p = 0.005). The same was shown for the subgroup of 44 endometriosis patients after endometrioma surgery when compared with controls (49.1% vs. 34.0%, p = 0.014). Clinical pregnancy rate was not higher in endometriosis but was close to significance (47.0% vs. 32.3%, p = 0.059) while live birth rate was comparable (27.3% vs. 32.3%, p = 0.746). Miscarriage rate was higher in the endometriosis group (19.7% vs. 7.3%, p = 0.018). A significantly higher AFC was observed in the control group in comparison with the endometriosis group (16.3 ± 7.6 vs. 13.4 ± 7.0, p = 0.014). Live birth rate did not differ when comparing all endometriosis cases (p = 0.746), ASRM Stage I/II and Stage III/IV (p = 0.348 and p = 0.888) with the control group but the overall pregnancy rate was higher in ASRM Stage I/II (p = 0.034) and miscarriage rate was higher in ASRM Stage III/IV (p = 0.030) versus control. Conclusion: Blastocyst transfers in women with endometriosis originate from cycles with lower AFC but higher share of mature oocytes than in control women, suggesting that endometriosis might impair ovarian reserve but not stimulation response. A higher miscarriage rate, independent of blastocyst quality may be attributed to an impact of endometriosis on the endometrium beyond the timing of implantation.

Uterine artery embolisation: fertility, adenomyosis and size - what is the evidence?

BACKGROUND: Uterine artery embolisation is well established as a treatment for symptomatic fibroids, however, there remain some uncertainties. We have carried out a focused literature review on three particularly challenging aspects - post-procedure fertility, symptomatic adenomyosis and large volume fibroids and uteri, to enable operators to utilise evidence-based guidance in patient selection, consent, and management. REVIEW: Literature searches were performed of the PubMed/Medline, Google scholar, EMBASE and Cochrane databases. The outcomes of our analysis of studies which recorded fertility rates in women desiring pregnancy following UAE for symptomatic fibroids found an overall mean pregnancy rate of 39.4%, live birth rate of 69.2% and miscarriage rate of 22%. The major confounding factor was patient age with many studies including women over 40 years who already have lower fertility compared to younger cohorts. Miscarriage rates and pregnancy rates in the studies analysed were comparable to the age matched population. Treatment of pure adenomyosis and adenomyosis with co-existing uterine fibroids with UAE has been shown to produce symptomatic improvement with better outcomes in those with combined disease. Although the effectiveness is not as high as it is in pure fibroid disease, UAE provides a viable and safe alternative for patients seeking symptom relief and uterine preservation. Our analysis of studies assessing the outcomes of UAE in patients with large volume uteri and giant fibroids (> 10 cm) demonstrate no significant difference in major complication rates demonstrating that fibroid size should not be a contraindication to UAE. CONCLUSION: Our findings suggest uterine artery embolisation can be offered to women desiring pregnancy with fertility and miscarriage rates comparable to that of the age-matched general population. It is also an effective therapeutic option for symptomatic adenomyosis as well as for the treatment of large fibroids > 10 cm in diameter. Caution is advised in those with uterine volumes greater than 1000cm3. It is however clear that the quality of evidence needs to be improved on with an emphasis on well-designed randomised controlled trials addressing all three areas and the consistent use of validated quality of life questionnaires for outcome assessment to enable effective comparison of outcomes in different studies.

Impact of Insulin Resistance on Ovarian Sensitivity and Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome Undergoing IVF.

BACKGROUND: Ovarian sensitivity index (OSI) is an accurate index to reflect the ovarian sensitivity to exogenous gonadotropins in in vitro fertilization (IVF). How insulin resistance (IR) affects OSI and pregnancy outcomes during IVF remains unclear. METHODS: This was a large retrospective, cohort study. A total of 2055 women with polycystic ovary syndrome (PCOS) undergoing the first fresh IVF cycle were enrolled. They were grouped into terciles based on the homeostasis model assessment of insulin resistance (HOMA-IR) values as control, medium and IR group for comparison. Multivariate regression analysis was also conducted. RESULTS: HOMA-IR had a significantly negative impact on OSI (adjusted ß = -0.24; 95% CI, -0.35 to -0.13), especially in lean patients with an adjusted ß of -0.33 (95% CI, -0.51 to -0.16). The interaction analysis revealed an interactive association between HOMA-IR and body mass index (BMI) (p = 0.017). IR was related to an increased early miscarriage risk independently with an odds ratio (OR) of 2.21 (95% CI, 1.13 to 4.33), without significant impact on pregnancy and live birth rate. CONCLUSION: IR decreased the ovarian response in PCOS patients undergoing IVF, especially in the lean subgroup. IR may result in a higher risk of early miscarriage, but did not impair pregnancy and live birth rate.

Impact of antibiotic treatment for chronic endometritis on pregnancy outcomes in women with reproductive failures (RIF and RPL): A systematic review and meta-analysis.

Objective: The aim of this study was to investigate the effect of antibiotic treatment for chronic endometritis (CE) on reproductive outcomes. Design: Systematic review and meta-analysis. Patients: Women with reproductive failures, including recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL). Interventions: Literature searches were performed using three electronic databases (PubMed, Embase, and Web of Science) until 1 December 2021 (without date restriction). The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with normal endometrial histology (negative for CE); and women with cured CE vs. women with persistent CE (PCE). The summary measures were indicated as odds ratio (OR) with a 95% confidence interval (CI). Main outcome measures: These include on-going pregnancy rate/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), and miscarriage rate/pregnancy loss rate (MR/PLR). Results: A total of 2,154 women (from twelve studies) were enrolled. Compared with the control group, women with CE receiving antibiotics did not show a statistically significant difference in OPR/LBR (P = 0.09) and CPR (P = 0.36), although there was a lower MR (P = 0.03). Women with cured CE have higher OPR/LBR (OR 1.57) and CPR (OR 1.56) in comparison with those with non-CE. There was a statistically significantly higher OPR/LBR (OR 6.82, P < 0.00001) and CPR (OR 9.75, P < 0.00001) in women with cured CE vs. those with persistent CE. Conclusion: While antibiotic treatment is a sensible option to cure CE, more well-designed prospective studies are needed to evaluate the reproductive impact of antibiotic treatment. Cured CE provides high-quality maternal conditions for subsequent embryo transfer and successful pregnancy.

Association of thyroid peroxidase antibodies with the rate of first-trimester miscarriage in euthyroid women with unexplained recurrent spontaneous abortion.

Background: Unexplained recurrent spontaneous abortion is a serious reproductive problem of unknown etiology. Thyroid peroxidase antibodies (TPO-Ab) may be associated with pregnancy outcomes in unexplained recurrent spontaneous abortion with normal thyroid function. Objective: This study aimed to investigate the relationship between TPO-Ab and the first trimester miscarriage rate/live birth rate in women of unexplained recurrent spontaneous abortion with normal thyroid function. Methods: We retrospectively analyzed the clinical data of 297 women who met our strict inclusion criteria, comparing the first trimester miscarriage rate/live birth rate between the TPO-Ab positive and TPO-Ab negative groups. For the same purpose, we also performed subgroup analysis. Results: Of the included women, 76 (25.6%) were TPO-Ab positive, and 221 (74.4%) were negative. First trimester miscarriage rate differed between the two groups (36.8% vs 24.0%, RR = 1.54, 95% CI: 1.05-2.24, P = 0.030). In the younger subgroup (<35 years) and the primary RSA subgroup, First trimester miscarriage rate was also higher in the TPO-Ab positive group (33.3% vs 19.0%, RR = 1.75, 95% CI: 1.07-2.87, P = 0.030; 36.5% vs 21.7%, RR = 1.69, 95% CI: 1.10-2.58, P = 0.020). While the live birth rate was lower in women with TPO-Ab positive, the difference did not reach statistical significance, even in the subgroup analysis. Conclusion: Our results suggest that TPO-Ab is associated with first trimester miscarriage rate in euthyroid women with unexplained recurrent spontaneous abortion.

Summer is not associated with higher live birth rates in fresh IVF/ICSI cycles: a population-based nationwide registry study.

STUDY QUESTION: Is summer associated with a higher live birth rate after fresh IVF/ICSI? SUMMARY ANSWER: There was no support for a higher live birth rate after fresh IVF/ICSI when treatment was performed during the summer season. WHAT IS KNOWN ALREADY: Seasonal variations in human natural conception and birth rates are well described. It has been hypothesized that serum vitamin D, levels of which are associated with sun exposure, may have a role in human natural conception rates. However, the association between seasons and IVF outcomes has not yet been clarified and conflicting reports have been published. Furthermore, it has been suggested that women with normal vitamin D levels have a better pregnancy outcome after ART compared to those with vitamin D insufficiency. STUDY DESIGN SIZE DURATION: A nationwide, register-based cohort study including all first-time fresh IVF/ICSI treatments (n = 52 788) leading to oocyte retrieval in Sweden between 2009 and 2018 was carried out. PARTICIPANTS/MATERIALS SETTING METHODS: All first-time fresh IVF/ICSI cycles leading to oocyte retrieval were identified in the National Quality Registry of Assisted Reproduction. Data collected included patient characteristics as well as information about the treatment cycle and pregnancy outcome. The patients were divided into season subgroups, (summer, autumn, winter and spring) based on the date of oocyte retrieval. The primary outcome was live birth rate, which was defined as the number of live births per oocyte retrieval and embryo transfer (ET). Other outcomes included clinical pregnancy per ET and miscarriage per clinical pregnancy. Logistic regression with multiple imputation was performed to evaluate whether there was an association between season and IVF/ICSI outcomes, with summer as reference. Adjustments were made for woman's age, year of treatment, BMI, total FSH/hMG dose, type of treatment, fertilization type, embryonic stage at ET and number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rate per oocyte retrieval ranged between 24% and 26% among seasons. A significantly higher live birth rate was seen for spring compared with summer, 26% versus 24%, respectively (adjusted odds ratio (OR) 1.08, 95% CI 1.02-1.16, P = 0.02). No significant association was seen when winter and autumn were compared with summer. Live birth rate per ET ranged between 29% and 31% among seasons. A significantly higher live birth rate was seen for spring and autumn compared with summer, at 31% and 31%, respectively versus 29% (adjusted OR 1.08, 95% CI 1.01-1.16, P = 0.04 and adjusted OR 1.09, 95% CI 1.01-1.16, P = 0.02), respectively. No significant association was seen when winter was compared with summer. Clinical pregnancy rate varied between 36% and 38% and miscarriage rate between 16% and 18%, with no significant seasonal associations. LIMITATIONS REASONS FOR CAUTION: Possible limitations are the retrospective design of the study and unmeasured confounders. Another limitation is that a generalized estimating equation (GEE) model was not used. The use of a GEE model would have made it possible to include all started fresh IVF/ICSI cycles since it allows for correction for any dependence between cycles within women. WIDER IMPLICATIONS OF THE FINDINGS: The results of this large registry study give no support for the hypothesis that IVF/ICSI treatments performed during summer season, with the highest degree of sunlight and vitamin D synthesis, is associated with higher pregnancy and live birth rates. In fact, our results showed significantly lower live birth rates during summer compared with spring and autumn. However, the magnitude of this difference was small and unlikely of clinical value. We suggest that season should not be taken into consideration when planning and performing fresh IVF/ICSI treatments. STUDY FUNDING/COMPETING INTERESTS: Financial support was received through the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70 940) and grants from the Hjalmar Svensson's Research Foundation (HJSV2021019 and HJSV2021037). None of the authors declare any conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Systematic review of subsequent pregnancy outcomes in couples with parental abnormal chromosomal karyotypes and recurrent pregnancy loss.

OBJECTIVE: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant management vs. preimplantation genetic diagnosis (PGD). DESIGN: Systematic review and meta-analysis. SETTING: Academic medical centers. PATIENT(S): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated. RESULT(S): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in couples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90-1.03; I2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I2 = 0). Compared with those who chose expectant management, differences in accumulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD. CONCLUSION(S): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management.

The relationship between TSH levels and clinical pregnancy outcomes for patients who undergo in vitro fertilization/intracytoplasmic sperm injection: a retrospective study.

Background: Thyroid dysfunction is linked with adverse pregnancy outcomes, an upper limit of a normal thyroid-stimulating hormone (TSH) threshold of 4.12-4.5 mIU/L should be considered for subclinical hypothyroidism in the infertile female population. Whereas, it's controversial whether or not the infertility thresholds for upper limit of TSH threshold of 2.5 mIU/L. In our study examines the correlation of optimal TSH levels and clinical pregnancy outcomes after fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) embryo transfer cycles. Methods: Patients who underwent fresh IVF/ICSI embryo transfer cycles for the first time who presented between January 1, 2015 and December 31, 2017 at the Chongqing Institute of Reproductive and Genetic, Chongqing Health Center for Women and Children were enrolled. We excluded patients with ≥40 years, body mass index (BMI) ≤18 or ≥28 kg/m2, the man with severe oligoasthenospermia, women with poor ovarian reserve, and presence of endocrine disorders, uterine anomaly, sactosalpinx, abnormal thyroid function, preimplantation genetic diagnosis, and chromosomal abnormality or polymorphism. Baseline characteristics and clinical pregnancy outcomes were observed in our study. We detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by Receiver operating characteristic (ROC) curves and logical regression. Results: A total of 6,088 patients who undergo IVF/ICSI were included. We first detected that the live birth rate had a statistically significant difference when the TSH level was 3 mIU/L. With the TSH ≤3 mIU/L group having a higher live birth rate than the TSH >3 mIU/L group (51.79% vs. 47.89%, P=0.024), meanwhile no significant difference were revealed between the early miscarriage rate (12.54% vs. 14.97%, P=0.091) and early clinical pregnancy rate (59.21% vs. 56.32%, P=0.114). There were no differences in pregnancy outcomes when the TSH threshold was at 3.5 or 4 mIU/L and no association was detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by ROC curves and logical regression. Conclusions: Patients undergoing IVF/ICSI with a serum TSH level ≤3 mIU/L may have a higher live birth rate rather than ≤2.5 or ≤4 mIU/L.

Reproductive Outcomes of In Vitro Fertilization and Fresh Embryo Transfer in Infertile Women With Adenomyosis: A Retrospective Cohort Study.

Background: Adenomyosis is commonly encountered in infertile women; however, it is still unclear whether adenomyosis has a detrimental effect on in vitro fertilization and embryo transfer (IVF-ET) outcomes. Method: We enrolled 1146 patients with adenomyosis and 1146 frequency-matched control women in a 1:1 ratio based on age, BMI, and basal follicle-stimulating hormone (FSH) level. After controlling for other factors, the rates of clinical pregnancy, miscarriage, live birth, and obstetric complications were compared between two groups. Results: There was no significant difference in clinical pregnancy rate between the two groups (38.1% vs. 41.6%; P=0.088). The implantation rate (25.6% versus 28.6%, P=0.027) and live birth rate (26% versus 31.5%, P=0.004) were significantly lower in the women with adenomyosis than in the controls. The miscarriage rate in the adenomyosis group was higher than that in the control group (29.1% versus 17.2%, P=0.001). After adjusting for confounding factors, multivariate analysis showed the clinical pregnancy rate was not statistically different between the two groups (OR: 0.852, P=0.070). In the adenomyosis group, the rate of miscarriage(OR: 1.877, P=0.000), placenta previa (OR: 2.996, P=0.042)and preeclampsia (OR: 2.287, P=0.042)were increased significantly, while live birth rate (OR: 0.541, P=0.000) was reduced significantly than control group. Conclusion: Adenomyosis has negative effect on IVF-ET outcomes in which miscarriage risk increased, live birth rate reduced and obstetric complications increased.

Does Choosing Microfluidics for Sperm Sorting Offer an Advantage to Improve Clinical Pregnancies in Donor Egg Recipients?

Background: Microfluidics (MF), an advanced sperm sorting technology results in the extraction of spermatozoa with higher DNA integrity and lower DNA damage compared to existing conventional sperm sorting methods. Aims: The aim of the present study is to assess the efficiency of MF and to isolate the best spermatozoa for intracytoplasmic sperm injection (ICSI) over the density gradient (DG) technique. Study Setting and Design: We recruited couples who choose the oocyte donation programme for this study to eliminate confounding factors associated with oocyte quality. Materials and Methods: Sperm was processed by MF (n = 180) and DG (n = 151). ICSI was performed and positive pregnancy, miscarriage and clinical pregnancy rates were compared. Statistical Analysis: All variables were analysed using Graph Pad Prism 5. The unpaired two-tailed t-test was used to assess the significance. A value of P < 0.05 was considered statistically significant. Results: There was no significant difference in pregnancy rates between the groups. However, a clear demarcation is seen in terms of clinical pregnancy rates, where the DG group achieved higher clinical pregnancies (91.7%) compared to the MF group (80.7%). Further, we compared miscarriage rates and biochemical pregnancies, and found a significantly higher miscarriage and biochemical pregnancy rate in the MF group (14.5% and 4%, respectively) compared to the DG group (6% and 1%, respectively). Conclusions: Based on the available literature, we anticipated a higher clinical pregnancy rate with MF compared with conventional processing. Our results show MF does not have any add-on positive effect on clinical pregnancy rate.

Effect of recombinant LH supplementation timing on clinical pregnancy outcome in long-acting GnRHa downregulated cycles.

BACKGROUND: Timely and moderate luteinizing hormone (LH) supplementation plays positive roles in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles with long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation. However, the appropriate timing of LH supplementation remains unclear. METHODS: We carried out a retrospective cohort study of 2226 cycles at our reproductive medicine centre from 2018 to 2020. We mainly conducted smooth curve fitting to analyse the relationship between the dominant follicle diameter when recombinant LH (rLH) was added and the clinical pregnancy outcomes (clinical pregnancy rate or early miscarriage rate). In addition, total cycles were divided into groups according to different LH levels after GnRHa and dominant follicle diameters for further analysis. RESULTS: Smooth curve fitting showed that with the increase in the dominant follicle diameter when rLH was added, the clinical pregnancy rate gradually increased, and the early miscarriage rate gradually decreased. CONCLUSIONS: In long-acting GnRHa downregulated IVF/ICSI-ET cycles, the appropriate timing of rLH supplementation has a beneficial impact on the clinical pregnancy outcome. Delaying rLH addition is conducive to the clinical pregnancy rate and reduces the risk of early miscarriage.

Does advanced paternal age affect outcomes following assisted reproductive technology? A systematic review and meta-analysis.

Infertility affects more than 14% of couples, 30% being caused by male factor infertility. This meta-analysis includes 28 studies, selected according to PRISMA guidelines. Data were extracted from these studies to collate cycles separating paternal age at 30, 35, 40, 45 and 50 years (±1 year). Primary outcomes of interest were clinical pregnancy, live birth and miscarriage rates. Secondary outcomes were the number of fertilized eggs, cleavage-stage embryos and blastocysts, and embryo quality per cycle. Fixed-effects and random-effects models giving pooled odds ratios (OR) were used to assess the effect of paternal age. This meta-analysis included a total 32,484 cycles from 16 autologous oocyte studies and 12 donor oocyte studies. In autologous cycles, a statistically significant effect of paternal age <40 years was noted in clinical pregnancy (OR 1.65, 95% confidence interval [CI] 1.27-2.15), live birth (OR 2.10, 95% CI 1.25-3.51) and miscarriage (OR 0.74, 95% CI 0.57-0.94) rates. Paternal age <50 years significantly reduced miscarriage rate (OR 0.68, 95% CI 0.54-0.86), and increased blastocyst rate (OR 1.61, 95% CI 1.08-2.38) and number of cleavage-stage embryos (OR 1.67, 95% CI 1.02-2.75) in donor oocyte cycles, where maternal age is controlled. This is an important public and societal health message highlighting the need to also consider paternal age alongside maternal age when planning a family.

Mitochondrial DNA Levels in Trophectodermal Cells Show No Association with Blastocyst Development and Pregnancy Outcomes.

Background: In patients undergoing assisted reproduction, levels of mitochondrial DNA (mtDNA) in the trophectodermal cells of the developing blastocyst are suggested to be associated with its ability to implant. However, discrepancies exist regarding the use of mtDNA levels as a reliable biomarker to predict outcomes of assisted reproduction. Aims: The aim of the study is to explore the association of trophectodermal mtDNA levels to determine blastocyst quality, implantation potential of blastocyst and clinical outcomes in couples who have undergone pre-implantation genetic testing for aneuploidy (PGT-A). Study Setting: Private fertility centre. Study Design: Retrospective analysis. Materials and Methods: We analysed mtDNA levels in the trophectodermal cells of 287 blastocysts from 61 couples undergoing PGT-A. The levels of mtDNA were estimated by next-generation sequencing method. mtDNA levels were correlated with maternal age, blastocyst morphology, ploidy status, implantation rates, miscarriage rate and live birth rate. Statistical Analysis Used: Linear regression and one-way ANOVA with Tukey's all column comparison test. Results: The trophectodermal mtDNA levels did not correlate with maternal age. There were no significant differences in their levels in grade 1 and grade 2 blastocysts. No significant differences were seen between mtDNA levels of implanted and non-implanted blastocysts or those blastocysts that resulted in miscarriage or live birth. However, significantly lower amounts of mtDNA were seen in euploid blastocysts as compared to that in aneuploid blastocysts. Conclusion: mtDNA levels in the trophectodermal cells of the blastocyst do not associate with blastocyst quality (grade 1 and grade 2), implantation potential and clinical outcomes but can differentiate between aneuploid and euploid blastocysts. Our study does not support the use of trophectodermal mtDNA levels as a biomarker for blastocyst quality and predictor of clinical outcomes.

Comparison of two endometrial preparation methods for frozen-thawed embryo transfer in anovulatory PCOS patients: Impact on miscarriage rate.

OBJECTIVE: Some studies have suggested that patients with polycystic ovary syndrome (PCOS) are at high risk of miscarriage. However, this still remains controversial. Several potential factors might explain this association: obesity, hyperinsulinemia and hyperandrogenism. Artificial and stimulated cycles appear to be comparable for endometrial preparation in frozen-thawed embryo transfer (FET) in PCOS patients. Only a few studies have assessed miscarriage rates specifically in PCOS. We have evaluated the impact of endometrial preparation on FET outcomes in anovulatory PCOS patients. METHODS: A retrospective cohort study was conducted at the Lille University Hospital, including 255 FET cycles in 134 PCOS patients between January 2011 and December 2017. PCOS was defined by the presence of at least two of the three Rotterdam's criteria. Patients were under 35 years old. Two endometrial preparation protocol were studied: stimulated cycle (gonadotropins on the second day of the cycle and luteal phase support including natural progesterone 600 mg/day) and artificial cycle (6 mg oral estradiol valerate and 800 mg micronized vaginal progesterone daily). RESULTS: 137 FET were performed under stimulated cycle and 118 FET under artificial cycle. Early pregnancy rates (30% versus 37.3%, p = NS), miscarriage rates (22% versus 25%, p = NS) and live birth rates (23.4% versus 26.3%, p = NS) were similar. CONCLUSIONS: In anovulatory PCOS women, the type of endometrial preparation does not influence FET outcomes, specifically regarding the miscarriage rate.