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In the last decade, fertility preservation has risen as a major field of interest, creating new interactions between oncologists and gynecologists. Various options, such as cryopreservation of ovarian tissue, have been developed and are currently routinely proposed in many centers. However, many of the options remain experimental and should be offered to patients only after adequate counseling. This paper addresses the efficiency and the potential of the different fertility preservation approaches.

Abstract Background The concept of using a gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin for triggering ovulation in patients treated with an antagonist protocol for in vitro fertilization (IVF) has become a routine clinical practice. It may promote oocyte nuclear maturation, resumption of meiosis and cumulus expansion. It seems that this attempt could be beneficial in an in vitro maturation (IVM) oocyte cycle performed for polycystic ovarian syndrome as well as for other indications such as urgent fertility preservation in patients with malignancies or unusual indications. Case presentation We present the case of a Caucasian patient who needed fertility preservation when routine natural IVF treatment did not yield oocyte retrieval, followed by three IVM cycles, priming ovulation with a GnRH-a. In total, 12 oocytes were obtained, all matured 4.5 hours after incubation in maturation media. The fertilization rate after intracytoplasmic sperm injection was 83%. Six good-quality embryos were vitrified. Conclusions It seems that triggering with a GnRH-a in selected cases may replace human chorionic gonadotropin in IVM of oocytes and could be highly beneficial in terms of obtaining high-grade embryos and possible pregnancy.

This prospective, case-control study evaluated the impact of obesity on oocyte quality based on mtDNA expression in cumulus cells (CC), and on bone morphogenetic protein 15 (BMP-15) and heparan sulfate proteoglycan 2 (HSPG2) in follicular fluid (FF). It included women 18 to <40 years of age, divided according to BMI < 24.9 (Group 1, n = 28) and BMI > 25 (Group 2, n = 22). Demographics, treatment, and pregnancy outcomes were compared. The mtDNA in CC, BMP-15, HSPG2, the lipid profile, the hormonal profile, and C-reactive protein were evaluated in FF and in blood samples. The BMP-15 levels in FF and the mitochondrial DNA in CC were higher in Group 1 (38.8 ± 32.5 vs. 14.3 ± 10.8 ng/mL; p = 0.001 and 1.10 ± 0.3 vs. 0.87 ± 0.18-fold change; p = 0.016, respectively) than in Group 2. High-density lipoprotein levels in blood and FF were higher in Group 1 (62 ± 18 vs. 50 ± 12 mg/dL; p = 0.015 and 34 ± 26 vs. 20.9 ± 7.2 mg/dL; p = 0.05, respectively). Group 2 had higher blood C-reactive protein (7.1 ± 5.4 vs. 3.4 ± 4.3 mg/L; p = 0.015), FF (5.2 ± 3.8 vs. 1.5 ± 1.6 mg/L; p = 0.002) and low-density lipoprotein levels (91 ± 27 vs. 71 ± 22 mg/dL; p = 0.008) vs. Group 1. Group 1 demonstrated a trend toward a better clinical pregnancy rate (47.8% vs. 28.6%: p = 0.31) and frozen embryo transfer rate (69.2% vs. 53.8; p = 0.69). Higher BMI resulted in lower BMP-15 levels and reduced mtDNA expression, which reflect decreased oocyte quality in overweight women.

This study evaluated β-human chorionic gonadotropin (hCG) changes during the early period of pregnancy in an attempt to predict successful pregnancy outcomes in ART. It determined the median values of the β-hCG and the 2-day β-hCG increments of clinical vs biochemical pregnancies. The results of fresh day 3 embryo, frozen day 3 embryo, and frozen day 5 embryo transfers were evaluated. The cutoff values of β-hCG and the 2-day increments predicting clinical pregnancy and delivery were determined. All women who underwent embryo transfer and had a singleton pregnancy from January 2017 to December 2019 were included. As expected, clinical pregnancies had higher initial median β-hCG values compared to biochemical pregnancies (fresh day 3 (400 vs 73 mIU/mL), frozen day 3 (600 vs 268.5 mIU/mL) and frozen day 5 (937 vs 317 mIU/mL)). Nonetheless, the abortion rate was significantly lower in the group with β-hCG above the cutoff values in fresh (141 mIU/mL) and frozen (354.5 mIU/mL) cleavage stage transfers (17.2% vs 44%, P < 0.001 and 18.5% vs 38%, P = 0.003, respectively). Blastocyst transfers resulted in higher median initial β-hCG compared to cleavage embryo transfers (937 vs 600 mIU/mL), and the initial β-hCG values from frozen cleavage embryos were higher compared to fresh cleavage embryos (600 vs 400 mIU/mL). Earlier implantation in frozen cycles may be caused by freezing-thawing procedures. Moreover, in fresh cycles, negative effects of the hormonal milieu of fresh cycles may delay implantation. These results indicate that high initial β-hCG and high 2-day β-hCG increments demonstrated better outcomes, including more clinical pregnancies and fewer abortions.

This prospective, observational study investigated the incidence of irregular cleavage (IRC) among human embryos and its influence on IVF treatment outcomes. It included 1001 women who underwent 1976 assisted reproduction treatments during 2016-2021 in a single IVF clinic. Embryo morphokinetics were analyzed and evaluated for the association between IRC and women's characteristics, treatment characteristics, and pregnancy outcomes. The incidence of IRC was 17.5% (1689/9632 embryos). Of these, 85% of the embryos had one IRC, 15% had multiple IRC and 35% of IRC events occurred during the embryo's first cell cycle. IRC embryos were found to correlate with male factor ( p = 0.01) and higher ICSI rate ( p = 0.01). Age, BMI, parity, basal FSH level, stimulation protocol, and number of retrieved oocytes did not differ between groups. Embryos with early IRC or more than one IRC had lower blastulation rates ( p = 0.01 for each). Fresh cycles with IRC embryos had a lower clinical pregnancy rate ( p = 0.01) and embryos with early IRC had a lower live birth rate ( p = 0.04) compared to embryos without IRC. Frozen transfer cycles of blastocyst embryos, with or without IRC, had comparable results. In conclusion, the number of abnormal cleavage events and their timing are important factors in the prognosis of the developing human embryo.

The effect of the luteinizing hormone (LH) elevation before the human chorionic gonadotropin (hCG) trigger in ovulatory frozen-thawed embryo transfer (Ovu-FET) cycles has not been determined. We aimed to investigate whether triggering ovulation in Ovu-FET cycles affects the live birth rate (LBR), and the contribution of elevated LH at the time of hCG trigger. This retrospective study included Ovu-FET cycles performed in our center from August 2016 to April 2021. Modified Ovu-FET (hCG trigger) and true Ovu-FET (without hCG trigger) were compared. The modified group was divided according to whether hCG was administered, before or after LH increased to > 15 IU/L and was twice the baseline value. The modified (n = 100) and true (n = 246) Ovu-FET groups and both subgroups of the modified Ovu-FET, those who were triggered before (n = 67) or after (n = 33) LH elevation, had comparable characteristics at baseline. Comparison of true vs. modified Ovu-FET outcomes revealed similar LBR (35.4% vs. 32.0%; P = 0.62), respectively. LBR were similar between the modified Ovu-FET subgroups regardless of the hCG trigger timing (31.3% before vs. 33.3% after LH elevation; P = 0.84). In conclusion, LBR of Ovu-FET were not affected by hCG trigger or whether LH was elevated at the time of hCG trigger. These results add reassurance regarding hCG triggering even after LH elevation., (© 2023. The Author(s).)

Research Question: Can mid-infrared attenuated total reflection (MIR ATR) spectroscopy combined with machine learning methods be used as an additional tool to predict embryo quality and IVF treatment outcomes?, Design: Spent culture media was collected and analysed. MIR ATR absorbance spectra were measured using an ALPHA II spectrometer equipped with an attenuated total reflection (ATR) spectrometry accessory. Patient and treatment data and results were collected and analysed in combination with machine learning techniques to identify possible correlations. The main outcome measures were to define the characteristics of absorbance spectra of spent culture media and to distinguish the difference in absorbance between top- and low-quality embryos, day 3 and day 5 embryos and implanting embryos versus non-implanting embryos., Results: Spent culture media of 227 embryos was collected and analysed. Absorbance peaks in the culture media were different between day 3 and day 5 embryos. Moreover, significant differences in P-values, spanning from 0.014 to 0.044 in absorbance peaks for day 3 embryos and 0.024 up to 0.04 for day 5 embryos, were seen between implanting and non-implanting embryos. Machine learning techniques offered a pregnancy prediction value of 84.6% for day 3 embryos., Conclusions: MIR ATR may offer an additional parameter for better selection of embryos based on the spectrometric absorbance and secretions of metabolites in the culture media., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Many risk factors can potentially influence sperm quality. Telomeres confer stability on the chromosome and their dysfunction has been implicated in conditions such as cancer, aging, and lifestyle. The impact of lifestyle on sperm cell telomeres is unclear. The objectives of this study were to evaluate the impact of lifestyle behaviors on telomere length in sperm and to follow the correlation with pregnancy outcomes in patients undergoing in vitro fertilization (IVF). In this prospective observational study, sperm was analyzed for telomere length (TL). Men were asked to report lifestyle behaviors including occupation (physical or sedentary), smoking duration and amount, physical activity, dietary habits, and where they keep their cellular phone (bag, pants, or shirt pocket). Correlations among semen analysis, TL, men's habits, and embryo quality and pregnancy outcomes were evaluated. Among 34 patients recruited, 12 had longer TL and 13 shorter TL. Sperm motility was negatively correlated with TL (Pearson correlation = -.588, p = .002). Smoking adversely affected native sperm motility (53% motility in nonsmokers vs. 37% in smokers; p = .006). However, there was no significant impact on TL. The group with longer telomeres demonstrated significant association with healthy diet (10/12 vs. 6/13; p = .05) and a trend toward more sports activity, weekly (16/84 vs. 7/91; p = .04) compared with the shorter telomeres group. This study suggests that lifestyle, healthy diet, and sports activity are associated with long telomeres in sperm. Sperm quality is also influenced by patients' habits. The study strongly recommends maintaining a healthy lifestyle to preserve general health and fertility.

Problem: The COVID-19 pandemic has many clinical manifestations. Rapid vaccine development raised concerns and speculations about future fertility outcomes and vaccine safety. We evaluated the effect of Pfizer-BioNTech mRNA SARS-CoV-2 vaccine on IVF treatment, oocyte and embryo quality, and pregnancy outcomes., Method of Study: This prospective, observational cohort study was conducted in a referral IVF Unit, 3/2021-5/2021. We aimed to recruit all women undergoing IVF/ICSI cycles from 3/1-4/30/2021, 2-8 weeks after the second vaccination, and to analyze 50-60 samples in the 2-month period. Patients were categorized according to serum antibody levels: positive for spike (S), positive for nucleotide (N), or negative for both. On the day of ovum pick-up, follicular fluid and blood samples were analyzed for anti-nucleotide (anti-N) antibodies, and anti-spike (anti-S) antibodies, hormonal profile, C-reactive protein (CRP) and other metabolic parameters., Results: Of 59 women enrolled, 37 reported being vaccinated and 22 were not. We found 97% correlation between anti-S and anti-N in the blood and the follicular fluid. Follicular fluid was analyzed based on antibody categorization. All IVF treatment parameters in the follicular fluids and serum were comparable, except CRP was significantly elevated among patients with anti-N antibodies (2.29 [1.42-6.08] vs. 4.11 [1.62-5.75] vs. 1.44 [.36-8.33]; p < .001). Pregnancy outcomes were comparable (44% vs. 33% vs. 50%; p = .97)., Conclusion: mRNA SARS-CoV-2 vaccine did not appear to affect treatment outcomes or ovarian reserves in the subsequent IVF cycle., (© 2022 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

This retrospective cohort study examined the effect of maternal BMI on embryo morphokinetics using a time-lapse incubator (TLI) and evaluated the effect on outcomes of frozen embryo transfer (FET) cycles. The study included 641 women who underwent FET of a total of 2553 embryos from January 2017 to August 2019. The women were divided into four groups according to BMI: underweight (<18.5 kg/m2), normal weight (18.5−24.99 kg/m2), overweight (25.0−29.99 kg/m2), and obese (≥30 kg/m2). Embryos were transferred on day 3 or 5, and their development was monitored using a TLI. We found that oocytes from obese patients were slower in the extraction of the second polar body (tPB2) after fertilization and the two pronucleus stage appeared later compared to normal-weight women. The time to fading of the pronucleus (tPNf), t2, and t4 were comparable between the four groups. Oocytes from underweight and overweight women had significantly faster cleavage at t3 and t5−t8 compared to normal weight. We did not find any significant difference in pregnancy rate, clinical pregnancy rate, or miscarriage rate among groups. In conclusion, embryos from normal-weight patients had slower cleavage rates compared to obese patients, while embryo quality was similar between BMI groups. The cycle outcomes demonstrated comparable pregnancy rates among the BMI groups.

Background: Fertility treatment discontinuation is difficult as it entails accepting childlessness. In most countries, financial limitations provide sufficient justification to terminate treatment. In Israel, unlimited funding enables women to undergo multiple treatment cycles, even when the odds of success are poor, thus providing a context for studying the psychological mechanisms involved when financial constraints are set aside. The study aimed to investigate the contribution of unrealistic optimism to Israeli women's willingness to continue fertility treatments even after repeated failures and to their psychological adjustment, comparing age groups., Methods: A longitudinal study of 100 women (ages 31-45) undergoing in vitro fertilization (IVF) treatment (1-22 previous cycles), who filled in questionnaires assessing their estimates of treatment success (theirs/for same-age patient), estimates received from the physician, intentions to continue treatment, and psychological adjustment. Follow-up was conducted 17(± 4) months later, by phone (n = 71) and/or medical records (n = 90)., Results: Most women (57%) reported that they will continue as long as needed till they have a child, 13% did not know, and 25% mentioned a specific plan; 5 did not reply. Women's estimates of treatment success showed vast unrealistic optimism, which was unrelated to their age, history of unsuccessful treatment cycles, or intentions for treatment continuation, yet was related to better psychological adjustment. At follow-up, almost all women who did not conceive were found to have continued treatments., Conclusions: Unrealistic optimism helps women maintain hope and well-being along the demanding journey to (biological) parenthood, where childlessness is highly stigmatized, and contributes to perseverance in treatment, regardless of objective factors., (© 2021. International Society of Behavioral Medicine.)

Background: Impaired paternal genome expression may cause poor embryonic development after in vitro fertilization (IVF)., Objective: To evaluate the expression of male infertility on embryo morphokinetics using a time-lapse incubator and its impact on IVF cycles., Materials and Methods: This retrospective cohort study followed patients from January 2017 to August 2019. Patients were divided according to the cause of infertility to male factor (study group) and unexplained infertility (control group) and further subdivided according to the severity of male infertility., Results: A cohort of 462 patients who underwent IVF cycles, with a total of 3,252 embryos was evaluated. Intracytoplasmic sperm injection (ICSI) was conducted more often in the study group compared to the control group (94% vs. 47%, p < 0.0001) and more embryos were discarded (47% vs. 43%, p = 0.016). Treatment outcomes were comparable in both groups regardless of the severity of male infertility. T3-T5 had a significant impact on embryo quality and more transfer and freeze compared to discard. Maternal age, number of aspirated oocytes, BMI, protocol used, and faster time to T3, T6 were significant in increasing chances of achieving pregnancy., Conclusion: The paternal genome may have an earlier impact on embryo development than previously surmised and may also account for faster morphokinetics. Faster embryo cleavage in male infertility IVF-ICSI cycles may contribute to outcomes comparable to other causes of infertility, in terms of embryo quality and clinical pregnancy rate, despite lower sperm quality, even in cases of severe Oligo-terato-Astheno spermia (OTA)., (© 2021 American Society of Andrology and European Academy of Andrology.)

This paper aims to study the efficacy and safety of diode laser hysteroscopic metroplasty for dysmorphic uterus and the impact on reproductive outcomes. This is a retrospective, single-center pilot study with prospective follow-up. The study was performed at a university-affiliated, tertiary hospital. From February 2018 to February 2020, all nulliparous women with a 3D ultrasound diagnosis of T-shaped or Y-shaped dysmorphic uterus and diagnosis of infertility, recurrent implantation failure, or recurrent pregnancy losses were referred for hysteroscopic metroplasty. Diode laser hysteroscopic metroplasty was performed under general anesthesia in an ambulatory setting. Main outcome measures included operative time, complications, hysteroscopic appearance of the cavity in a follow-up hysteroscopy, and reproductive outcomes in terms of pregnancy and live birth. A total of 25 infertile women with mean duration of infertility of 56.6 ± 36.1 months underwent hysteroscopic metroplasty. No complications were reported, and subsequent 3D ultrasound and follow-up hysteroscopic appearance were satisfactory in all cases. Maximum follow-up was 32 months (mean ± standard deviation 11.5 ± 9.2 months). Fifteen nulliparous women returned for fertility treatments in our institute, among whom nine conceived (60% pregnancy rate). The rate of deliveries and ongoing pregnancies (pregnancies beyond 24 weeks of gestation) was 78% (7/9), with six successful liveborn deliveries at 36-38 weeks and one ongoing pregnancy. One had spontaneous abortion at week 19 and one had a spontaneous abortion at week 7. Hysteroscopic metroplasty in an ambulatory setting, using diode laser, is a safe and effective procedure, improving reproductive outcomes in cases of T-shaped or Y-shaped uterus., (© 2021. Society for Reproductive Investigation.)

Data regarding association between early embryo development and maternal age is limited and inconclusive. This study has two aims: to evaluate differences in the cleavage stage of embryos in young versus advanced maternal age (AMA) women. To compare the early embryonic development of embryos that result in pregnancy versus no pregnancy. A retrospective study of early embryonic development which was recorded and analyzed using time-lapse imaging was conducted. The kinetic markers of time to pronuclei fading (tPNf) and appearance of two to eight cells (t2-t8) were assessed. For embryos cultured to blastocyst, times to morula (tM), start of blastulation (tSB) cavitated, and expanded blastocyst (tB, tEB) were also recorded. A total of 2021 oocytes from 364 intracytoplasmic sperm injection (ICSI) cycles were evaluated, of which 1223 (60.5%) were derived from young patients and 798 (39.5%) from those of AMA. The mean time points to t3, t4, t5, t6, tSB, tB, and tEB were significantly shorter for embryos derived from younger women, as compared to older women (p < 0.05). Overall, women who conceived presented a faster embryonic development, for both age groups. The mean time points of t2 and t8 were significantly shorter in patients who conceived versus not conceived (p < 0.05). We concluded that older women's age is associated with delayed embryonic development. Embryos that yielded pregnancy cleaved faster compared to those which did not, in both age groups. Thus, when considering which embryo to transfer to women of AMA, selecting the faster-developing embryos may improve the chances of conception., (© 2021. Society for Reproductive Investigation.)

This retrospective study was conducted to determine whether using oral dydrogesterone (DYD) instead of micronized vaginal progesterone (MVP) in frozen embryo transfer (FET) cycles affects pregnancy outcomes. Women undergoing autologous FET in an academic fertility center were evaluated. Uses of 10 mg TID oral DYD or MVP for patients treated in FET cycles (artificial and ovulatory cycle, separately) were compared. The main outcome measure was live birth rates in each group. The study analyzed 599 cycles that occurred from January 2018 through December 2019. Chemical and clinical pregnancy rates were comparable between DYD vs. MVP groups (41.6% vs. 38.1%; P = 0.44 and 36.7% vs. 31.4%; P = 0.18, respectively). The ongoing pregnancy and delivery rates (29% vs. 22%, P = 0.06), as well as abortion rate (12.3% vs. 15.8%, P = 0.2), were comparable between the two groups. In a case-control sub-analysis of artificial FET cycles, we found comparable results between the two modes of luteal support. Similarly, results were comparable in ovulatory cycles using these medications for luteal support. Chemical and clinical pregnancy rates were comparable with DYD vs. MVP, in artificial FET (33.7% vs. 34.8%; P = 0.89 and 27.7% vs. 27.5%; P = 1), and in ovulatory FET (46.5% vs. 43.9%; P = 0.71 and 42.3% vs. 38.2%; P = 0.53), respectively. Our results indicate that in FET, pregnancy outcomes with oral DYD were not inferior to those with MVP.

The aim of this study is to compare two different needles (17G vs. 20-17G variable diameter) used for OPU and to assess whether the different stress forces along the needle affect the presence of degenerative oocytes, oocyte quality, and embryo morphokinetics. Prospective, randomized study enrolled women undergoing in vitro fertilization (IVF) intracytoplasmic sperm injection (ICSI) from August 2016 through August 2018 in an IVF unit at a tertiary care medical center. Ovaries were randomly aspirated using either a 20-17G needle or a 17G needle. The embryologist was blinded to the aspirating needle and sibling oocytes were separated according to needle used for fertilization and further evaluation. Oocytes were scored negatively if one of the following parameters was abnormal immediately after OPU: polar body shape, zona pellucida, cytoplasm, perivitelline space, or vacuoles. The presence of degenerative oocytes was noted at OPU. A total of 580 oocytes from 43 women were evaluated, 293 in the 17G needle group and 287 in the 20-17G group. Oocyte scoring was comparable between the two different needles (- 1.99 ± 1.9 vs. - 1.88 ± 1.69; P = 0.13), as were embryo quality and pregnancy rate. Cohorts with degenerative oocytes had lower oocyte scores (- 2.11 ± 1.81 vs. - 1.60 ± 1.50; P = 0.001) and poorer performance and fertilization rates (62.5% vs. 78.5%; P < 0.001) than did cohorts with no degenerative oocytes. Cycles with degenerative oocytes in the cohort at OPU demonstrated poorer oocyte quality and decreased fertilization, regardless of the needle used. 1.5.2016 NIH number NCT02749773.

Objective: To evaluate the relationship between endometrial thickness measured before embryo transfer, and pregnancy outcomes in frozen-thawed embryo transfer (FET)., Methods: We retrospectively analyzed outcomes of all consecutive FET cycles, from January 2012 to August 2018. Based on ROC analysis for endometrial thickness, we found 8 mm was a reliable cutoff point to predict pregnancy prior to embryo transfer. Accordingly, the cycles were divided into Group A: cycles with endometrial thickness ≤ 8 mm and Group B: > 8 mm., Results: Group A included 485 FET cycles and group B included 626 cycles. Compared with group A, Group B had significantly higher chemical and clinical pregnancy rates (30.3 vs. 24.6%; p  = .046, and 24.0 vs. 18.6%; p  = .036), respectively. In multivariate analysis, endometrial thickness and the protocols used were the only parameters influencing the chance to achieve pregnancy, with odds ratio 1.54 (95%CI 1.07-2.22, p  = .019) for the endometrium and odds ratio 1.95 (95%CI 1.31-2.9; p = .001) to the protocol used. Endometrial thickness might predict crown-rump length (CRL) discordancy with odds ratio 4.61 ( p  = .001; 95% CI 1.42-14.92). Compared with group B, Group A had more cases of overt discordancy (13.3 vs. 4%; p  = .016)., Conclusions: For patients undergoing FET cycles, endometrial thickness and treatment protocol may predict the chemical and clinical pregnancy rates, as well as CRL discordancy., Summary: Endometrial thickness and preparation improved pregnancy rate in FET cycles and significantly greater crown-rump length discordancy was observed with thinner endometria.

This study evaluated which endometrial preparation protocol in frozen embryo transfer (FET) cycles provides the best results for polycystic ovarian syndrome (PCOS) patients and the general population. This retrospective study of 634 FET cycles was conducted 2016-2018. Cycles were divided into Group A: Artificial endometrial preparations for FET (aFET; n = 348), Group B: Ovulatory cycle ( n = 286) to compare two methods of endometrial preparation for FET. Artificial endometrial preparation with exogenous estrogen and progesterone versus natural ovulation cycles, modified natural cycles using hCG for the final triggering and letrozole-induced ovulation with hCG. Anovulatory patients were analyzed separately. Anovulatory PCOS patients had significantly higher pregnancy rates with letrozole treatment compared with aFET cycles (44% vs. 22.5%; p = 0.044). For the entire cohort, ovulatory cycles and aFET were similar in terms of patient characteristics, demographics, infertility causes, treatment protocols and number of embryos transferred. Although the mean ESHRE score of the transferred embryos was higher in the aFET group, we found higher clinical pregnancy rate in the ovulatory cycle FET (41.3% vs. 27.3%, p < 0.0001). A better pregnancy rate was found after ovulatory cycle FET. In the ovulatory cycles, the outcome of letrozole-induced and non-induced cycles were comparable. PCOS patients, as well as the general population, may benefit from ovulation induced FET cycles, with significantly better outcomes in FET in ovulatory cycles.

Aim: To find a cut-off ratio of estradiol/metaphase II oocyte (E2/M2) ratio and to evaluate the correlation with patients' characteristics, embryo morphokinetics using EmbryoScope™ and IVF cycle outcomes., Material and Methods: For this retrospective cohort study, records of all fresh cycles that were cultured and scored by EmbryoScope™ were evaluated. The peak E2/M2 ratio was calculated on the day of human chorionic gonadotropin (hCG) administration and correlated to embryo morphokinetic quality and cycle outcomes. A receiver operating characteristics analysis was calculated for the E2/M2 ratio and clinical pregnancy rates., Results: A total of 2461 oocytes were collected from 319 patients. Receiver operating characteristics analysis revealed a cutoff of 204 as a discriminative point to predict clinical pregnancy with a sensitivity of 69.5% and specificity of 62.1% (P < 0.001). E2/M2 > 204 group were older, had higher E2 concentration, fewer M2 oocytes despite elevated gonadotrophin doses. E2/M2 ratio ≤ 204 was correlated with higher fertilization rate, better embryo quality, higher pregnancy and live birth rates, and more frozen embryos., Conclusion: E2/M2 ratio < 204 yielded the best probability to achieve good quality embryos with good morphokinetic scores and better pregnancy outcomes and may be used to predict IVF cycle outcomes. Advanced maternal age and low ovarian response received higher concentrations of gonadotrophins, which resulted in higher E2/M2 ratio. Milder stimulation to those patients may improve their cycle outcomes.

Background: Maternal administration of magnesium sulfate (Mg) is used in humans to protect the fetal brain during preterm delivery. We sought to determine the neuroprotective mechanism of Mg in a rat model of late gestation maternal inflammation. Methods: Pregnant rats at 20 d of gestation (20 total, four groups, N  = 5 in each group) received i.p. LPS or saline. Dams were randomized for s.c. saline or Mg supplementation 2 h prior and following the LPS/saline injections. Dams were sacrificed 4 h following the last treatment. Fetal brains were collected from the four treatment groups. Fetal brain caspase 3 active form, NF-kB p65, neuronal nitric oxide synthase (phospho-nNos), and proinflammatory cytokines levels were determined by western blot. Results: Maternal LPS at e20 significantly ( p  < .01) increased fetal brain caspase 3 active form (af) (0.27 ± 0.02 versus 0.15 ± 0.06u), NFkB (0.23 ± 0.01 versus 0.13 ± 0.01u), and phospho-nNOS (0.22 ± 0.01 versus 0.12 ± 0.01u) and fetal brain proinflammatory cytokines (IL-6 0.21 ± 0.01 versus 0.11 ± 0.01 u; TNFα 0.29 ± 0.01 versus 0.15 ± 0.01u), compared with control fetuses. Mg treatment significantly ( p  < .05) reduced fetal brain caspase 3 af (0.16 ± 0.01u), NFkB p65 (0.11 ± 0.01u), phospho-nNOS (0.1 ± 0.01u), as well as brain proinflammatory cytokines (IL-6 0.07 ± 0.01u; TNFα 0.15 ± 0.01u) to levels similar to controls. Conclusion: Maternal inflammation-induced fetal brain injury at late gestation may be mediated by the activation of inflammatory response, oxidative stress, and apoptosis. Maternal Mg may attenuate the injury by inhibition of these putative pathways.

The presence of Degenerated Oocyte (DEG) was mostly described after intracytoplasmic sperm injection (ICSI), with fewer reports on DEG at the time of ovum pick-up (OPU). This study aims to assess morphokinetics of embryos cultured in a time-lapse incubator and compare cohorts with and without DEG at OPU. In a retrospective cohort study from January 1, 2016 until September 31, 2017 a total of 399 IVF/ICSI cycles and 2980 embryos were evaluated. In 81 of 399 cycles at least one DEG oocyte was observed at the time of OPU. The remaining 318 cycles with no DEG oocyte were compared as a control group. In the DEG group, significantly more oocytes were collected per patient (12.9 ± 7.2 vs. 10.1 ± 6.1. P < 0.001). Fertilization rate, pregnancy and clinical pregnancy rates were comparable between the two groups, however, the morphokinetics and developmental scores of the embryos were significantly worse in the DEG group, (KID 3.4 ± 1.6 vs. 3.2 ± 1.6 P = 0.002 and ESHRE 1.5 ± 1.1 vs. 1.4 ± 1.0 P = 0.046). Significantly more patients achieved top-quality embryos in the NON DEG group (58.8% vs. 53.0%, P = 0.03), however, comparable delivery rate was achieved in both groups. In the DEG group, the frequency of DEG oocyte per cycle was negatively correlated with pregnancy rate. GnRH agonist protocol and the 17-20G needle used for OPU were significant predictors for the presence of DEG oocyte at OPU. In conclusions DEG oocyte may negatively affect IVF outcome, however, younger patients, and significantly more oocytes collected in the DEG group compensate for the IVF results.

Background: Lipids are an important source for energy production during oocyte maturation. The accumulation of intracellular lipids binds to proteins to form lipid droplets. This may lead to cellular lipotoxicity. The impact of lipotoxicity on cumulus and granulosa cells has been reported. This pilot study evaluated their correlation to oocyte and embryo quality., Design: Prospective case-control study., Setting: Referral IVF unit., Patients: Women younger than age 40, undergoing IVF with intracytoplasmic sperm injection., Interventions: 15 women with BMI > 30 (high BMI) and 26 women with BMI < 25 (low BMI) were enrolled. IVF outcomes were compared between groups based on BMI. Lipid content in cumulus and granulosa cells was evaluated using quantitative and descriptive methods. Lipid profile, hormonal profile and C-reactive protein were evaluated in blood and follicular fluid samples. Demographic and treatment data, as well as pregnancy rates were collected from electronic medical records., Results: Higher levels of LDL and CRP, slower cell division rate and lower embryo quality were found in the group with high BMI. There was no difference in pregnancy rates between groups. In light of these findings, treatment outcomes were reanalyzed according to patients who became pregnant and those who did not. We found that patients who conceived had significantly lower fat content in the granulosa cells, reflected by mean fluorescence intensity recorded by flow cytometry analysis (23,404 vs. 9370, P = 0.03)., Conclusions: BMI has no effect on lipid content in cumulus and granulosa cells, and does not affect likelihood of pregnancy. However, women who achieved pregnancy, regardless of their BMI, had lower lipid levels in their granulosa cells. This finding is important and further study is needed to evaluate lipid content in granulosa cells as a potential predictor of IVF treatment success.

Objective: To report the efficacy of combined systemic and local methotrexate treatment for cesarean scar pregnancy and review data from selected, similar case series., Study Design: A retrospective case series of 12 patients with cesarean scar pregnancy treated in a university hospital between 2014 and 2018. The intervention was combined treatment of systemic and local methotrexate., Results: Twelve patients were treated with combined systemic and local methotrexate. Clinical characteristics, clinical course and treatment efficacy were evaluated. Mean gestational age at diagnosis was 7.5 weeks (range 5.9-9.1). βhCG levels at diagnosis ranged from 1581 to 345,427 U/L with a mean of 77,795 U/L. All 12 patients were successfully treated without surgical intervention and with no significant side-effects. Mean hospitalization duration was 9 days (5.8-12.6) and mean time to normalization of βhCG levels was 98 days (63-132)., Conclusions: Treatment of cesarean scar pregnancy with a combination of systemic and local methotrexate was effective and safe. Although the treatment course tends to be longer than with other modalities, this protocol offers excellent success rates, with fertility preservation and few complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To examine the effect of serum follicle-stimulating hormone (sFSH) level, body-mass index (BMI) and smoking on Testicular Sperm Extraction-Intracytoplasmic Sperm Injection (TESE-ICSI), and pregnancy outcomes.In this retrospective study, data were extracted from files of 52 azoospermic men who underwent TESE and in-vitro fertilization (IVF)-ICSI in our IVF unit. Demographic information, treatment cycle follow-up and pregnancy outcomes were collected.Fifty-two patients underwent 79 TESE due to azoospermia in 143 IVF cycles. Smoking was found to significantly affect sperm motility in TESE specimens before freezing (45.5% vs 14.8%; P <.001); however, this finding did not influence the pregnancy rate. Male FSH was inversely correlated with testicle volume (r = -0.595, P <.0001). Body weight did not affect semen parameters after TESE or ICSI outcomes.Among azoospermic patients with extremely poor sperm quality, male BMI, male FSH or smoking did not have an adverse effect sperm parameters or pregnancy and delivery rates.

Purpose: Excess maternal inflammation and oxidative stress while in utero have been known to affect gross fetal development. However, an association between the inflammatory process in utero and the effects on ovarian development and future fertility has not yet been demonstrated. This study focused on LPS-induced chronic inflammation in early pregnancy and its effect on ovarian development and reserves of the offspring, using a rat model. Our aim was to determine whether maternal inflammation in utero disturbs reproductive system development in the offspring, given that maternal inflammation and oxidative stress has been shown to affect gross fetal development., Methods: Prospective case control rat model. Sprague-Dawley pregnant rats (n = 11) received intraperitoneal lipopolysaccharide (LPS group) (50 µg/kg bodyweight) or saline solution (control group) on day 14, 16, and 18 of gestation. Pups were delivered spontaneously. At 3 months, female offspring were weighed and killed. Ovaries were harvested for (1) follicle count using hematoxylin and eosin staining, (2) apoptosis: ovaries were stained for caspase, and (3) serum CRP and AMH levels were determined., Results: Birth weights of pups were significantly lower in the LPS group compared to the control group (6.0 ± 0.6 vs. 6.6 ± 0.4 gr; P = 0.0003). The LPS group had fewer preantral follicles, and increased intensity of Caspase 3 staining (510 vs. 155.5 u; P = 0.007). AMH levels were significantly lower in the LPS group (4.15 ± 0.46 vs 6.08 ± 1.88 ng/ml; P = 0.016). There was no significant difference in the CRP and MCP-1 levels between the two groups., Conclusions: Chronic maternal inflammation induced intrauterine growth restriction in offspring and a decrease in the proportion of follicles. This change might be due to premature apoptosis. These preliminary results suggest that maternal inflammation has a detrimental effect on the development of the female reproductive system of the offspring and thus, future fertility.

Background: Obesity is associated with several fertility disorders. This prospective cohort study was designed to evaluate the effect of body mass index (BMI) (kg/m 2 ) on oocyte diameter and treatment., Methods: Women undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) were enrolled in the study. They were divided into two groups according to BMI: obese (BMI > 30) and normal weight (BMI < 25). Mature oocytes were evaluated according to total diameter, zona pellucida, and oolema diameters., Results: A total of 387 oocytes were obtained from the 46 women who participated. Significantly more mature oocytes (M2) were retrieved from normal weight patients compare to obese women (15.1 ± 6.8 vs. 9.7 ± 3.9, respectively, P < 0.001). Oocytes from women in the obese group were significantly smaller than those in the normal weight group, including oocyte diameter (157.9 ± 7.9 vs. 164.3 ± 5.1 μm, P < 0.0001), oolema diameter (110.3 ± 4.5 vs. 113.5 ± 3.5 μm, P < 0.0001), and zona pellucida thickness (17.9 ± 2.6 vs. 19.0 ± 2.4 μm, P < 0.000), respectively. Multivariate logistic regression analysis, including oolema diameter, female age, BMI, number of M2 oocytes, and zona pellucida, was conducted to predict pregnancy. Small oolema diameter in obese patient adversely correlated with pregnancy. Larger oolema diameter was positively associated with the probability of pregnancy in the obese group as well as thinner zona pellucida., Conclusion: Obesity is associated with smaller oocytes, which adversely affect fertility outcomes., Trial Registration: NIH number NCT01672931.

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.

Background: Maternal magnesium administration has been shown to protect the preterm fetus from white- and gray-matter injury, although the mechanism is unknown., Objective: The purpose of the study is to test the following hypotheses: (1) maternal infections/inflammation activate fetal neuronal N-methyl-D-aspartate receptors that up-regulate neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells pathways; and (2) maternal magnesium sulfate attenuates fetal brain neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells activation through N-methyl-D-aspartate receptors., Study Design: Pregnant rats at embryonic day 16 and embryonic day 18 (n = 6, 48 total) received injections of intraperitoneal lipopolysaccharide 500 μg/kg or saline at time 0. Dams were randomized for treatment with subcutaneous magnesium sulfate (270 mg/kg) or saline for 2 hours prior to and following lipopolysaccharide/saline injections. At 4 hours after lipopolysaccharide administration, fetal brains were collected from the 4 treatment groups (lipopolysaccharide/saline, lipopolysaccharide/magnesium sulfate, saline/magnesium sulfate, saline/saline), and phosphoneuronal nitric oxide synthase, nuclear factor kappa-light-chain-enhancer of activated B cells p65, and chemokine (C-C motif) ligand 2 protein levels were determined by Western blot. An additional group of pregnant rats (n = 5) received N-methyl-D-aspartate-receptor antagonist following the lipopolysaccharide injection to study magnesium sulfate protective mechanism., Results: Lipopolysaccharide (lipopolysaccharide/saline) significantly increased fetal brain phosphoneuronal nitric oxide synthase, nuclear factor kappa-light-chain-enhancer of activated B cells p65, and chemokine (C-C motif) ligand 2 protein levels compared to the saline/saline group at both embryonic day 16 (phosphoneuronal nitric oxide synthase 0.23 ± 0.01 vs 0.11 ± 0.01 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.24 ± 0.01 vs 0.14 ± 0.01 U; chemokine (C-C motif) ligand 2 0.28 ± 0.01 vs .01 ± 0.01 U) and embryonic day 18 (phosphoneuronal nitric oxide synthase 0.28 ± 0.01 vs 0.12 ± 0.01 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.12 ± 0.01 vs 0.1 ± 0.01 U; chemokine (C-C motif) ligand 2 0.27 ± 0.01 vs 0.11 ± 0.01 U). Magnesium sulfate treatment to lipopolysaccharide dams (lipopolysaccharide/magnesium sulfate) significantly decreased fetal brain phosphoneuronal nitric oxide synthase, nuclear factor kappa-light-chain-enhancer of activated B cells, and chemokine (C-C motif) ligand 2 protein levels compared to lipopolysaccharide/saline dams at both embryonic day 16 (neuronal nitric oxide synthase 0.17 ± 0.02 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.17 ± 0.03 U; chemokine (C-C motif) ligand 2 0.18 ± 0.01 U) and embryonic day 18 (phosphoneuronal nitric oxide synthase 0.1 ± 0.01 U; nuclear factor kappa-light-chain-enhancer of activated B cells 0.09 ± 0.01 U; chemokine (C-C motif) ligand 2 0.21 ± 0.01 U). Notably, maternal lipopolysaccharide at embryonic day 16 activated nuclear factor kappa-light-chain-enhancer of activated B cells twice as often compared to dams induced at embryonic day 18. N-methyl-D-aspartate-receptor antagonist decreased fetal brain phosphoneuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells levels comparable to magnesium sulfate., Conclusion: Lipopolysaccharide-simulated inflammation during pregnancy may cause brain injury through activation of neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells pathways and, potentially, production of excitotoxic nitric oxide and inflammatory mediators. The increased susceptibility to brain injury in preterm fetuses may be due to enhanced nuclear factor kappa-light-chain-enhancer of activated B cells activation. Magnesium sulfate protective effects may be secondary, in part, to inhibition of neuronal nitric oxide synthase and nuclear factor kappa-light-chain-enhancer of activated B cells activation and decrease proinflammatory cytokine production through blocking nuclear factor kappa-light-chain-enhancer of activated B cells receptors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Highly purified Human Menopausal Gonadotropins (hp-hMG) and recombinant FSH (rFSH) are widely used in assisted reproductive technology (ART). The aim of this study was to compare ART results of the two preparations in GnRH antagonist cycles., Methods: In this retrospective cohort study, IVF antagonist cycles performed from 2011 through 2013 were reviewed. There were 508 antagonist cycles: 320 stimulated with rFSH and 188 with hp-hMG. For every hp-hMG, two rFSH were matched for patient's age and infertility diagnosis. Subgroup analysis of patients younger and older than 35 was done as well., Results: Both treatments were resulted in comparable pregnancy and live birth rates. However, cumulative pregnancy rates were higher for the rFSH group. In the matching analysis, the rFSH group had more mature oocytes and more embryos while using lower doses of gonadotropins. Pregnancy, cumulative pregnancy rates, and live birth rates were comparable. In the subgroup analysis, young patients in the rFSH group had better cycle outcomes compared with those in the hp-hMG group., Conclusion: In antagonist protocol, different gonadotropin products are equally effective. The choice of one or the other should depend on the availability, convenience of use, and cost.

Objective: To evaluate the effect of dilation and curettage (D&C) and misoprostol as treatments for spontaneous miscarriage (SM) on in vitro fertilization (IVF) parameters in the subsequent IVF cycle., Design: Multicenter, retrospective, cohort study. Women treated for SM after IVF treatment with D&C or misoprostol and underwent a subsequent IVF cycle was included. The main outcome measures were ovarian response, endometrial thickness and pregnancy rate in the subsequent IVF cycle after MA., Results: Among 73 patients with miscarriage, 41 had D&C and 32 were given misoprostol. Baseline serum follicle stimulating hormone (FSH) levels and ovarian responses before and after treatment of miscarriage were comparable. No significant differences were observed between the D&C and the misoprostol groups in basal FSH levels, endometrial thickness and parameters of ovarian response in the subsequent IVF cycle., Conclusion: D&C and misoprostol are both effective treatments for IVF patients with miscarriage, without an adverse effect on subsequent IVF treatment outcome.

Objective: Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate., Study Design and Methods: A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level., Main Results: One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7 ± 923.2 vs. 1342.9 ± 1223; P = 0.003 and 0.48 ± 0.31 vs. 0.83 ± 0.87; P = 0.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top-quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC = 0.632, p = 0.02 and 95 % CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45., Conclusion: Endometrial receptivity is determined by the complex interactions of E2 and P.

Objective: Spermatozoal morphology was reported to effect fertilization, embryo quality and pregnancy results in spontaneous conception and ART. Intracytoplasmic morphologically selected sperm injection (IMSI) is an innovative, not invasive technique, which examines the sperm with no harm at a magnification of 6000 × in order to obtain optimal sperm to perform IVF-ICSI. We evaluated the efficiency of IMSI technique in patients with repeated IVF-ICSI failure of at least three cycles with no viable pregnancy and/or very poor sperm quality., Study Design and Methods: All couples who performed IMSI between the years 2009 to 2012 were enrolled retrospectively to the study. Couples with male infertility who were treated with IMSI were included in the study. All their treatments were evaluated and divided into two subgroups: conventional IVF-ICSI treatment and their subsequent IMSI treatment. Demographic data, clinical parameters and outcome were recorded. The IMSI treatments were compared to previous non-IMSI treatments in terms of fertilization rates, cleavage rates, number of embryos and their quality, number of embryos transferred and pregnancy outcome., Main Results: Forty-two couples were reviewed. Basic characteristics of the groups were comparable. Fertilization and cleavage rates of the two groups were comparable. The embryos quality demonstrated a trend toward superior quality (grade 1-2) embryos in the IMSI versus ICSI (60% versus 47%; p = 0.07 and 53% versus 40%; p = 0.07), respectively. Implantation and clinical pregnancy rates were significantly superior in IMSI group (19.2% versus 7.8%; p = 0.042 and 41.3% versus 10.5%; p = 0.02, respectively). Miscarriage rate was significantly higher in conventional IVF-ICSI group (100% versus 15.8%; p = 0.04), and live birth rate was significantly higher in IMSI group (0 in conventional IVF-ICSI and 34.7% per transfer in IMSI group; p = 0.003)., Conclusion: IVF outcome of IMSI resulted in a higher implantation rate, pregnancy rate and most importantly delivery rate compare to non IMSI treated cycles.

Objective: Patients with polycystic ovarian syndrome (PCOS) are at increased risk of ovarian hyperstimulation syndrome (OHSS) in controlled ovarian hyperstimulation cycles. Interventions to reduce the risk of OHSS in these patients include in-vitro fertilization (IVF) with a gonadotropin-releasing hormone (GnRH) antagonist, and retrieval of immature oocytes followed by in-vitro maturation (IVM). The aim of this study was to compare the outcomes of IVM and IVF-GnRH antagonist protocols in women with PCOS undergoing assisted reproductive technology., Study Design: Retrospective cohort study. Records of women with PCOS who underwent IVM or IVF-GnRH antagonist protocols between 2010 and 2011 were reviewed. In total, there were 61 IVM cycles and 53 IVF-GnRH antagonist cycles. The treatment protocols were compared in terms of the number of oocytes retrieved, dose of gonadotropin administrated, fertilization rates, quality of embryos, pregnancy, and delivery and abortion rates., Results: The number (mean±standard deviation) of mature oocytes did not differ significantly between the two groups (7.11±5.7 vs 8.16±5.07 for the GnRH antagonist group and the IVM group, respectively; p=0.38). The average dose of gonadotropin (1938 IU±838 IU/cycle vs 118±199 IU/cycle; p<0.001), fertilization rate (77% vs 60%; p<0.001) and high-quality embryo rate (58.8% vs 48.3; p<0.001) were significantly higher in the GnRH antagonist group compared with the IVM group. Pregnancy rates (40% vs 25%; p=0.08), livebirth rates per pregnancy (71% vs 53%; p=0.265) and abortion rates (10% vs 27%; p=0.17) were comparable., Conclusions: The IVM protocol can be an alternative for infertile women with PCOS who wish to prevent the potential adverse effects of gonadotropin treatment. Prospective studies are needed to compare the outcomes of these two treatment protocols., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Objective: To evaluate pregnancy-related leading follicles during ovulation induction and superovulation with clomiphene citrate (CC) or gonadotropin., Design: Retrospective cohort., Patients: Five hundred and forty-two women who underwent a total of 615 treatment cycles with CC or gonadotropin., Intervention: We evaluated the effects of CC and gonadotropin on the leading follicles, clinical pregnancy rates and miscarriage rate., Results: The number of follicles larger than 15 mm in the different protocols was comparable. In those treated with CC, the diameter of the dominant follicles before human chorionic gonadotropins (hCG) trigger in the conception cycles (20.4 ± 1.2 mm) was significantly larger than in the non-conception cycles (18.8 ± 1.9 mm). In women treated with gonadotropin, the diameter of the leading follicle in the conception cycles (18.5 ± 1.7 mm) was comparable to that in the non-conception cycles (18.2 ± 1.7 mm). The pregnancy-related diameter of the leading follicle in CC cycles (20.4 ± 1.2 mm) was significantly larger than that in gonadotropin cycles (18.8 ± 1.9 mm; p = 0.001; 95% CI, -2.2 to -0.9)., Conclusion: Pregnancy-related diameter of the leading follicle in CC cycles is significantly larger than that in gonadotropin cycles and the best time for hCG trigger in the CC cycle is when the leading follicle reaches 20 mm.