Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes.

OBJECTIVE: To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. METHODS: A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. RESULTS: The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. CONCLUSIONS: The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients.

STUDY QUESTION: What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER: The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5-99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY: The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION: An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93-1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58-1.21, P = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5-99.6%). LIMITATIONS, REASONS FOR CAUTION: Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS: Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

High ovarian responders have the highest risk of premature progesterone rise.

OBJECTIVE: Late follicular phase progesterone elevation is a complication that affects approximately 38% of IVF cycles. There is a lack of consensus on the appropriate cut-off levels for progesterone on hCG day. Although premature progesterone rise occurs in all kinds of ovarian responses, there is a knowledge gap regarding the ovarian response with the highest risk of this phenomenon. Our study aims to assess the relative risk of each kind of ovarian response for premature progesterone rise and evaluate the prevalence of premature progesterone rise in each ovarian response. METHODS: A retrospective, cross-sectional, comparative and analytic study was performed at the Reproductive Endocrinology Department in Centro Médico Nacional 20 de Noviembre in Mexico City. All conventional-antagonist cycles were grouped according to their ovarian response and were evaluated from 2015 to 2020. Pearson's Squared-chi, Cramer's V, cross-table and the relative risk were calculated. RESULTS: The prevalence of premature progesterone rise oscillated from 20.8 to 67.9% for low and high ovarian responders, respectively. After calculating the relative risk, high ovarian responders had a 1.38 higher risk for premature progesterone rise than other groups. CONCLUSIONS: High ovarian responders have the highest risk for premature progesterone rise compared to normal and low ovarian responders. High ovarian responders have a 67.9% prevalence of premature progesterone rise.

Outcomes between non-IVF and IVF treatment after laparoscopic conservative surgery of advanced endometriosis with Endometriosis Fertility Index score >3.

Surgical excision of advanced endometriosis has been demonstrated to improve women's pain symptoms and quality of life in women in randomized placebo-controlled trials, but there is no strong evidence regarding the live birth rate. The revised American Fertility Society (r-AFS) classification for endometriosis has a limited predictive ability for fertility outcomes after surgery; therefore, EFI scoring has been advised for predicting conception after endometriosis surgery. No randomized controlled trials have investigated fertility outcomes in patients with advanced endometriosis after surgery. This study aimed to determine the outcomes of in vitro fertilization (IVF) or non-IVF treatments after conservative surgery for advanced endometriosis in patients with good prognosis Endometriosis Fertility Index (EFI) scores (>3). This prospective cohort study was conducted between April 2014 and April 2019 at a tertiary research hospital. In total, 113 women with suspected preoperative advanced endometriosis were enrolled in this study. A total of 90 women with advanced endometriosis underwent laparoscopic surgery. Fourteen patients with EFI score of ≤3 and 3 of them who had bilateral tubal occlusion were also excluded. Seventy-three women were included in this study. The remaining 30 women in the non-IVF group and 32 women in the IVF group were analyzed. The main outcome measures were cumulative pregnancy rates and live birth rates in both groups. Women who underwent IVF treatment were older than women (30 ±â€…3.41) who had non-IVF treatment (26.5 ±â€…3.07) after laparoscopic surgery (P < .001). The remaining baseline characteristics of the patients in both groups were similar. Clinical pregnancy, abortion, and live birth rates were similar in both the groups after 36 months of follow-up. This study demonstrated that cumulative pregnancy and live birth rates were similar to those of non-IVF or IVF treatments after conservative surgery for advanced endometriosis, if patients had good prognosis EFI scores. Furthermore, non-IVF treatments resulted in nearly the same clinical pregnancy results as IVF treatment within 1 year after surgery.

Effect of previous wedge resection for interstitial pregnancy on pregnancy and neonatal outcomes following frozen-thawed embryo transfer (FET) cycles of IVF/ICSI: a retrospective study.

OBJECTIVE: The present study aimed to evaluate pregnancy and neonatal outcomes in women, with a previous history of wedge resection for interstitial pregnancy, in frozen-thawed embryo transfer (FET) cycles of IVF/ICSI. METHODS: The present study involved a retrospective case-control assessment of 75 cases and 375 control subjects over 6 years in a single center. To compare pregnancy and neonatal outcomes between cases, treated using wedge resection, and controls without any previous history of ectopic pregnancy, propensity score matching (1:5) was utilized. The study also compared subgroups in the case group. RESULTS: Women with previous wedge resection exhibited higher rates of ectopic pregnancy and uterine rupture rate as compared to control subjects (9.1% vs 1.3%, P = 0.025 and 4.5% vs 0%, P = 0.035, respectively). No statistically significant differences were recorded between the two cohorts with regard to clinical pregnancy rate, live birth rate, and neonatal outcomes. For pregnancy type subgroup analysis, Z-score and rates of large for gestational age were recorded to be significantly lower in twin pregnancy subgroup when compared with singleton pregnancy subgroup (0.10 (- 0.59, 0.25) vs 0.50 (- 0.97, 1.39), P = 0.005; 4.5% vs 26.1%, P = 0.047, respectively). CONCLUSION: The results of the present study indicated that previous wedge resection correlated to a higher risk of ectopic pregnancy and uterine rupture. However, it might not be related to an increased risk of adverse neonatal outcomes. The study recommended cesarean section in these patients. Further studies are required to verify the validity of current recommendations.

A Premature Rise of Luteinizing Hormone Is Associated With a Reduced Cumulative Live Birth Rate in Patients ≥37 Years Old Undergoing GnRH Antagonist In Vitro Fertilization Cycles.

This is a retrospective cohort study included 1021 patients underwent a flexible GnRH antagonist IVF protocol from January 2017 to December 2017 to explore the effect of a premature rise in luteinizing hormone (LH) level on the cumulative live birth rate. All patients included received the first ovarian stimulation and finished a follow-up for 3 years. A premature rise in LH was defined as an LH level >10 IU/L or >50% rise from baseline during ovarian stimulation. The cumulative live birth rate was calculated as the number of women who achieved a live birth divided by the total number of women who had either delivered a baby or had used up all their embryos received from the first stimulated cycle. In the advanced patients (≥37 years), the cumulative live birth rate was reduced in patients with a premature rise of LH (ß: 0.20; 95% CI: 0.05-0.88; p=0.03), compared to patients (≥37 years) without the premature LH rise. The incidence of premature LH rise is associated with decreased rates of cumulative live birth rate in patients of advanced age (≥37 years) and aggravated the reduced potential of embryos produced by the advanced age, not the number of embryos.

GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve.

Objective: To evaluate the efficiency and validity of cessation of cetrorelix on trigger day during gonadotropin releasing hormone antagonist (GnRH-ant)-controlled ovarian stimulation of in vitro fertilization (IVF) cycles. Methods: In this retrospective study, a total of 1271 patients undergoing initial IVF cycles following the GnRH-ant protocol were enrolled; 832 patients received cetrorelix on trigger day (Group A) and 439 patients ceased cetrorelix on trigger day (Group B). We compared demographic characteristics, embryological and clinical outcomes between the two groups. A Poisson regression model was used to identify factors that significantly affected embryological outcomes. Patients were further divided into subgroups according to anti-Mullerian hormone (AMH) and age, to assess associations between ceasing cetrorelix on trigger day and embryological outcomes. Results: There was a significant improvement on embryological outcomes in patients who ceased cetrorelix on trigger day, and there were no significant differences in clinical outcomes or preovulation rates between the two groups. Furthermore, for patients with 1.1 ≤ AMH ≤ 4.7 ng/ml, all embryological outcomes were significantly higher in Group B compared with Group A. For patients with AMH > 4.7 ng/ml, the number of oocytes retrieved, fertilization rate (2PN) of IVF cycles and proportion of day 3 good quality embryos were all significantly higher in Group B. For patients with age < 35 years, all the embryological outcomes, besides the number of available embryos, were significantly higher in Group B than in Group A. There were no differences in embryological outcomes between the two groups when patients were stratified based on age > 35 years or AMH < 1.1 ng/ml. Conclusion: GnRH-ant protocol with cessation of cetrorelix on trigger day improved embryological outcomes for young patients or patients with sufficient ovarian reserve, and was effective at preventing preovulation.

Impact of human papillomavirus infection on semen parameters and reproductive outcomes.

BACKGROUND: Human papillomavirus (HPV) has been shown to adversely affect human reproduction. We aimed to evaluate the prevalence of human papillomavirus (HPV) infection in men and its correlation with semen parameters and reproductive outcomes. METHODS: Semen samples and penile swabs were collected from potential sperm donors (SD, n = 97) and male partners of infertile couples (IM, n = 328). The presence of HPV DNA in semen samples and penile swabs was analyzed. Associations between hrHPV positive status and fertility outcomes as well as socio-behavioral and health characteristics were evaluated using the R software package. RESULTS: High-risk HPV (hrHPV) genotypes were detected in 28.9% of SD and 35.1% of IM (P = 0.312). Penile swabs were more frequently positive for hrHPV genotypes than semen samples in both IM (32.3% vs. 11.9%, P < 0.001) and SD (26.8% vs. 6.2%, P = 0.006). Men with hrHPV positive semen samples had lower semen volume (median volume 2.5 ml vs. 3 ml, P = 0.009), sperm concentration (median concentration 16 × 106/ml vs. 31 × 106/ml, P = 0.009) and total sperm count (median count 46 × 106 vs. 82 × 106, P = 0.009) than men with hrHPV negative samples. No association was identified between penile hrHPV status and semen parameters. CONCLUSIONS: Our findings indicate that penile HPV infection is common in both potential sperm donors and men from infertile couples. Although HPV positivity is higher in penile swabs, only HPV infection in semen samples affects sperm parameters. However, there was no association between hrHPV positivity in semen and fertility outcomes including abortion rate.

Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study.

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

IVF embryo choices and pregnancy outcomes.

OBJECTIVE: Investigate the chromosome status and transfer outcomes of embryos selected using routine "best morphology" IVF practices. METHOD: A prospective multi-center, non-selection cohort study involving patients undertaking IVF treatment. Study entry conditions were blastocyst biopsy, >1 embryo with chromosome analysis and frozen transfer of the best morphology embryo. Primary analyses were ßhCG positive, implantation, ongoing pregnancy and birth rates and pregnancy-stage progression failures. RESULTS: After transfer, embryo chromosome status was assigned and outcomes divided into two primary groups - euploids (n = 135) and aneuploids (n = 53). Compared to euploid embryo transfers, aneuploid embryos had significantly lower primary outcomes (+ßhCG: 67% vs. 30%, p < 0.0001; IR: 56% vs. 19%, p < 0.0001; ongoing week 12: 51% vs. 9%, p < 0.0001; and livebirths: 50% vs. 8%, p < 0.0001, respectively). Transfers were further subdivided into smaller groups according to their main chromosomal feature. Stage analysis showed higher failure rates for aneuploids to initiate a pregnancy (p < 0.0001), higher subclinical miscarriage rate (p = 0.0402) and higher clinical miscarriage rate (p = 0.0038). CONCLUSION: Routine morphology-based embryo selection resulted in a high euploid selection rate but a significant number of aneuploid embryos were still inadvertently selected for transfer (28%) with the subsequent high failure rates for pregnancy initiation and progression having implications for appropriate patient management.

Effect of age and morphology on sustained implantation rate after euploid blastocyst transfer.

RESEARCH QUESTION: What impact does maternal age and embryo morphology have on sustained implantation rates of euploid blastocysts? DESIGN: This was a retrospective analysis of sustained implantation rates of euploid blastocysts stratified by maternal age and morphology. The primary analysis included 208 embryo transfers with a total of 229 embryos transferred from January 2017 through August 2020. RESULTS: For all ages the sustained implantation rates for day 5 good quality blastocysts were higher than for day 5 fair, day 5 poor and day 6 blastocysts. At a maternal age of 36 years the best-fit sustained implantation rates were 86% for day 5 good quality blastocysts, 64% for day 5 fair, 63% for day 5 poor, and 51% for all day 6 blastocysts analysed as one group. When controlling for morphology and day of biopsy, there were higher sustained implantation rates for euploid embryos of younger patients compared with older patients. The best-fit sustained implantation rates for age 33 compared to age 39 years were 86% versus 80% for day 5 good, 71% versus 62% for day 5 fair, 59% versus 55% for day 5 poor, and 81% versus 46% for all day 6. CONCLUSIONS: There was a clinically significant higher sustained implantation rate at all ages for euploid day 5 good quality embryos compared with day 5 fair, day 5 poor and day 6 embryos.

A comprehensive evaluation of progestin-primed ovarian stimulation protocol in patients with or without PCOS undergoing in vitro fertilization.

Progestin-primed ovarian stimulation (PPOS) regimen was established for assisted reproduction. However, its feasibility and outcomes in polycystic ovary syndrome (PCOS) patients need further evaluation. The outcomes of infertile patients with PCOS (study group) and normal ovaries (control group with unexplained infertility and tubal factor infertility) who underwent PPOS and IVF/ICSI protocol were retrospectively studied. The baseline information, primary, and secondary outcomes of patients were collected. The dynamic changes of hormones were closely monitored. 198 PCOS patients and 374 controls were included in this study. After controlled ovarian hyperstimulation (COH), 15 oocytes were retrieved from PCOS patients on average, which was more than those from the controls (p < 0.001). The oocytes and embryos obtained from the PCOS patients exhibited better developmental potential as the number of fertilized oocytes, cleaved embryos, top-quality embryos, viable embryos, cryopreserved embryos, the rate of fertilization, and viable embryo per oocyte retrieved in PCOS patients were significantly higher than those in the controls (all p < 0.001). No significant difference between the two groups was identified regarding the primary outcome, ongoing pregnancy, and other secondary outcomes. No moderate to severe ovarian hyperstimulation syndrome (OHSS) was diagnosed in either group. With the proposed PPOS protocol, the quantity, quality, developmental potential of oocytes, and embryos obtained from PCOS patients were superior to those from controls. The protocol was efficient and safe in terms of pregnancy, obstetric, and perinatal outcomes. OHSS was effectively mitigated in the patients, with or without PCOS, who underwent COH.

Impact of Thyroid Autoimmunity on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes and Fetal Weight.

Several studies have reported the association between thyroid autoimmunity (TAI) and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes. However, the findings remain controversial. We performed a large-scale retrospective cohort study to verify the effect of the presence of thyroid antibodies on IVF/ICSI outcomes and fetal growth and to evaluate the association between the types and titers of thyroid antibodies and adverse IVF/ICSI outcomes. A total of 16481 patients with infertility were referred to the Reproductive Center of Peking University Third Hospital for their first IVF/ICSI treatment between January 2018 and June 2019.Patients who sought IVF/ICSI treatment due to tubal or male factors infertility and who achieved fresh embryo transfer were included in our study. Finally, 778 patients with thyroid antibody positivity were selected as the TAI group, and 778 age-matched patients were included in the control group. The number of oocytes retrieved and high-graded embryos and the rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were compared between the TAI and control groups. In addition, subgroup analysis was performed to demonstrate whether different types and titers of thyroid antibodies had different effects on IVF/ICSI outcomes. After adjusting for thyroid function, anti-Müllerian hormone levels, basal follicle stimulating hormone levels, basal estradiol levels and antral follicle count, the number of oocytes retrieved in the TAI group was significantly lower than that in the control group. No significant differences were observed between the two groups in the rates of clinical pregnancy, miscarriage, preterm delivery, live birth, and birth weight in singletons; however, the birth weight in twin pregnancy was significantly lower in the TAI group than in the control group. Subgroup analysis showed no association between the types or titers of thyroid antibodies and adverse IVF/ICSI outcomes. In conclusion, the presence of TAI in patients with infertility did not impair embryo quality or affect pregnancy outcomes, including clinical pregnancy, miscarriage, preterm delivery, and live birth. However, it decreased the number of oocytes retrieved and birth weight in twin pregnancy.

IVF impact on the risk of recurrence of endometrial adenocarcinoma after fertility-sparing management.

RESEARCH QUESTION: Do IVF treatments after conservative management of endometrial atypical hyperplasia or grade 1 endometrial adenocarcinoma (AH/EC) increase the risk of disease recurrence? DESIGN: This is a prospective cohort study from a national registry from January 2008 to July 2019. Sixty patients had an AH/EC and received progestin treatment using chlormadinone acetate for at least 3 months. After remission, 31 patients underwent IVF and 29 did not. The primary outcome was the recurrence rate at 24 months according to the use of IVF. The secondary outcome was the identification of risk factors for recurrence. RESULTS: The probability of 2-year recurrence was 37.7% (SD 10.41%) in the IVF group and 55.7% (SD 14.02%) in the no IVF group (P = 0.13). Obesity, nulliparity, polycystic ovary syndrome, age and tumoural characteristics were not associated with recurrence. Pregnancy was a protective factor for recurrence, with 2-year recurrence probabilities of 20.5% and 62.0% in the pregnancy and no pregnancy groups, respectively (P = 0.002, 95% CI 0.06-0.61). In contrast, the number of cycles, maximum serum oestradiol concentration during ovarian stimulation, ovarian stimulation protocol, total dose of gonadotrophin administered and thickness of the endometrium showed no significant differences in terms of the risk of recurrence in the IVF subgroup. CONCLUSION: IVF treatment after fertility-sparing management of AH/EC does not increase the risk of recurrence. Therefore, it is an acceptable strategy to decrease the time to pregnancy. Overall, the recurrence rate is high enough to justify close monitoring once remission occurs.

Kallistatin in follicular fluid of women with endometriosis and its correlation with IVF outcome.

BACKGROUND: Endometriosis (EM) affects 10% women of reproductive age and alters fertility. Its management is still debated notably the timing of surgery and ART in infertility. Kallistatin (KS) is an endogenous protein that regulates differential signaling pathways and biological functions. However, the function and the underlying molecular mechanism in EM and its correlation with in vitro fertilization (IVF) outcome have not been determined. The purpose of this study was to evaluate KS concentrations in follicular fluid (FF) of women with EM and controls women without EM who underwent IVF with embryo transfer (IVF-ET). METHODS: FF KS concentrations from 40 patients with EM and 40 non-EM patients were measured by ELISA. RESULTS: Compared with the non-EM patients, patients with EM had lower KS levels in FF (281.67 ± 104.60 vs. 490.70 ± 216.33 pg/ml). The rates of fertilization (61.64 ± 22.42 vs. 71.00 ± 24.39%), available embryo (45.96 ± 19.83 vs. 50.61 ± 26.26%), and top-quality embryo (12.71 ± 21.01 vs. 16.04 ± 16.87%) were significantly lower in the EM group than in the control group. The KS concentrations in the FF of women who conceived consequent to the treatment were significantly higher than those from women who did not in the combined EM and control groups. CONCLUSIONS: These results indicate that the KS concentration in FF could be used as a predictor for IVF-ET outcomes. This may contribute to the pathologic mechanism responsible for the poor outcome of IVF in patients with EM.

How far is too far? Does time interval between GnRH antagonist and GnRH agonist trigger in GnRH antagonist cycles matter?

RESEARCH QUESTION: What is a suitable time interval between the last GnRH antagonist exposure and GnRH agonist (GnRHa) triggering for final follicular maturation? DESIGN: A retrospective cohort study including 413 patients undergoing GnRH antagonist cycles in which GnRHa trigger was used, either solely or as a dual trigger. The primary outcome measure was the follicle/mature oocyte ratio. Cycles were analysed according to the time interval between the last GnRH antagonist exposure and the GnRHa triggering: Group 1 included patients with a 12-14 h interval; Group 2: 7-10 h interval; Group 3: 5-6 h interval and Group 4: 2-4 h interval. LH concentration was measured 11-13 h post-GnRHa injection. RESULTS: Median LH value was 65 IU/l. There was a weak but significant correlation between basal LH and the LH surge (R2 = 0.137, P < 0.001). Although square root LH values differed significantly between study groups (P < 0.001; higher in Groups 2 and 3), the follicle/mature oocyte ratio was not different across the four antagonist-agonist interval groups and no correlation was detected between the post-trigger LH concentration and the follicle/oocyte ratio (R2 = 0.011). In a model integrating age, day 3 FSH concentration, maximal oestradiol and body mass index along with the study groups, none of these factors was significantly related to the follicle/mature oocyte outcome ratio. Insufficient surge (LH < 15 IU/l) occurred in 14 (3.4%) cases. Rates of insufficient LH surge did not differ significantly between the groups (2.4%, 3.2%, 3.4% and 7.1% in Groups 1 to 4, respectively; P = 0.5). CONCLUSIONS: LH concentrations post-GnRHa trigger differ in regard to antagonist-agonist intervals, but the follicle/mature oocyte ratio achieved was not affected.

Anti-Müllerian hormone level may predict successful pregnancy after adenomyomectomy in patients with infertility due to adenomyosis.

ABSTRACT: We aimed to determine clinical factors predicting successful pregnancy by comparing pregnancy failure and success groups after adenomyomectomy. Additionally, we analyzed fertility outcomes after adenomyomectomy.The medical records of 43 patients who had undergone adenomyomectomy and received in vitro fertilization treatment from 2017 to 2020 were retrospectively reviewed. Patients were divided into pregnancy failure (n = 28) and pregnancy success (n = 15) groups. Patients' demographic factors were evaluated and compared between the groups.The age of patients was higher (39.0 [32.0-45.0] vs. 37.0 [33.0-42.0] years, P = .006) whereas the level of anti-Müllerian hormone (anti-Müllerian hormone [AMH]; 0.54 [0.01-8.54] vs. 2.91 [0.34-7.92] ng/mL, P = .002) lower in the pregnancy failure group compared to the pregnancy success group. The operative time was longer (220.0 [68.0-440.0] vs. 175.0 [65.0-305.0] min, P = .048) while the estimated blood loss higher (750 [100-2500] vs. 500 [50-2000] mL, P = .016) in the pregnancy failure group compared to the pregnancy success group. No significant difference was observed in body mass index, symptoms, cancer antigen 125, preoperative uterine volume, or type of adenomyosis. In the multivariate analysis, age and AMH were significant predictive factors for successful pregnancy.Ovarian reserve (age and AMH) and disease severity might be predictive factors for successful pregnancy in patients who have undergone adenomyomectomy. Adenomyomectomy should be considered for women desiring pregnancy and having appropriate ovarian reserve. Our results would be beneficial for patients and clinicians before deciding on adenomyomectomy. Larger prospective studies are required to confirm our findings.

Risk factors for the development of endometrial fluid in women undergoing IVF: A retrospective cohort study✰.

RESEARCH QUESTION: Presence of endometrial fluid (EF) is a poorly understood pathology and remains a challenge for clinicians, as very little data exists to explain its consequences and treatment. Our objective was to investigate risk factors for EF during IVF. DESIGN: This retrospective cohort study included all women with a freeze all embryos cycle (FAE) for EF between 2010 and 2016 at a university-affiliated private IVF center. Controls (2:1) were randomly selected out of the database of our fresh autologous IVF cycles during the same period. Main outcome measures were possible risk factors for EF, comprising polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), previous pelvic or endometrial surgery (polypectomy or synechia removal), cesarean section, myomas and severe endometriosis. A logistic regression model was used to assess independent risk factors for EF. RESULTS: Out of 9000 IVF cycles, 1204 were FAE cycles, among which we identified 86 EF cases. We then selected 171 controls. Independent risk factors for presence of EF were a history of previous myomectomy (adjusted odds ratio (aOR) 19.77, 95%CI [4.01-97.53]), severe endometriosis (aOR 5.97, 95%CI [2.09-17.05]), PCOS (aOR 5.72, 95%CI [2.66-12.33]) and previous cesarean section (aOR 5.17, 95%CI [1.84-14.49]). CONCLUSIONS: Our results are not only confirming the association between PCOS, severe endometriosis, previous cesarean procedure and EF, but also reporting for the first time an association between previous myomectomy and EF.

Impact of thyroid cancer treatment on assisted reproductive technology outcomes in women with infertility.

PURPOSE: We investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes. METHODS: This retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed. RESULTS: We found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity. CONCLUSION: Our study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.

"The Back-up Vasectomy Reversal." Simultaneous Sperm Retrieval and Vasectomy Reversal in the Couple With Advanced Maternal Age: A Cost-Effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of different fertility options in men who have undergone vasectomy in couples with a female of advanced maternal age (AMA). The options include vasectomy reversal (VR), sperm retrieval (SR) with in vitro fertilization (IVF), and the combination of VR and SR with IVF, which is a treatment pathway that has been understudied. MATERIALS AND METHODS: Using TreeAge software, a model-based cost-utility analysis was performed estimating the cost per quality-adjusted life years (QALY) in couples with infertility due to vasectomy and advanced female age over a period of one year. The model stratified for female age (35-37, 38-40, >40) and evaluated four strategies: VR followed by natural conception (NC), SR with IVF, VR and SR followed by failed NC and then IVF, and VR and SR followed by failed IVF and then NC. QALY estimates and outcome probabilities were obtained from the literature and average patient charges were calculated from high-volume centers. RESULTS: The most cost-effective fertility strategy was to undergo VR and try for NC (cost-per-QALY: $7,150 (35-37 y), $7,203 (38-40 y), and $7,367 (>40 y)). The second most cost-effective strategy was the "back-up vasectomy reversal": undergo VR and SR, attempt IVF and switch to NC if IVF fails. CONCLUSION: In couples with a history of vasectomy and female of AMA, it is most cost-effective to undergo a VR. If the couple opts for SR for IVF, it is more cost-effective to undergo a concomitant VR than SR alone.