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OBJECTIVE: To investigate the potential impact of vitamin D (VD) serum levels on couples going through in vitro fertilization treatment in terms of embryo quality and pregnancy rates. DESIGN: A retrospective cohort study. SETTING: A private human reproduction center. PATIENT(S): A total of 267 couples underwent intracytoplasmic sperm injections between January 2017 and March 2019. INTERVENTION(S): The couples were categorized into four groups on the basis of 25-hydroxy VD (25OHD) levels measured at the beginning of the stimulation protocol: group 1 with 25OHD levels ≥30 ng/mL for both women and men; group 2 with 25OHD levels <30 ng/mL for both; group 3 women with 25OHD levels <30 ng/mL and men with 25OHD levels ≥30 ng/mL; and group 4 with women with 25OHD level ≥30 ng/mL and men with 25OHD level <30 ng/mL. MAIN OUTCOME MEASURE(S): We consider the quantity and quality of embryos during the cleavage as well as blastocyst stages as primary outcomes. Correspondingly, the clinical pregnancy rate (CPR) was regarded as a secondary outcome. RESULT(S): Our findings revealed no significant correlations between the studied VD groups and the evaluated outcomes. This includes the quantity and quality of embryos during the cleavage and blastocyst stages, as well as the CPR. Primary analysis revealed a small but statistically significant difference in the duration of controlled ovarian stimulation between group 1 and group 2 (95% confidence interval, 0.07-3.04) and between group 1 and group 3 (95% confidence interval, 0.05-3.23). CONCLUSION(S): The present study found no correlation between the studied VD levels and the quantity as well as quality of cleavage or blastocyst stage embryos, nor did it show any impact on CPRs. Further well-designed, prospective studies are warranted to determine whether and how vitamin D affects reproductive outcomes.

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The aim of this study was to evaluate the effects of medroxyprogesterone acetate (MPA) treatment in comparison to those of gonadotropin releasing hormone (GnRH) antagonists for the prevention of premature luteinizing hormone surges during controlled ovarian hyperstimulation (OS) and the impact of these effects on developing embryos and pregnancy outcomes. Data from 757 cycles of GnRH antagonist treatment and 756 cycles of MPA treatment were evaluated at the Akdeniz University Faculty of Medicine Assisted Reproductive Treatment Center between October 2018 and April 2022. Patient records were obtained from the electronic database of the centre and analysed. In our centre, GnRH antagonist protocols were used between 2018 and 2020, and MPA protocols were used between 2020 and 2022. We chose our study population by year. Our study is a comparative retrospective study. All methods in this study were performed in accordance with the relevant guidelines and regulations. Patients using MPA were significantly older (33.9 ± 5.6 vs. 32.6 ± 5.6, p < 0.001) and had a lower number of antral follicles (AFC) (10.7 ± 8.6 vs. 11.9 ± 10.8, p = 0.007) than those using GnRH antagonists. Both MPA (2.9%) and GnRH antagonists (2.2%) had similar effectiveness in preventing premature ovulation (p = 0.415). There was no significant difference between the two groups in terms of the number of total developed embryos (1.3 ± 1.3 vs. 1.2 ± 1.2, p = 0.765). There was no significant difference in the clinical pregnancy rates with the first ET (%35.4 vs. %30.1, p = 0.074), per total number of transfers (35.3% vs. 30.1%, p = 0.077). MPA was found to be effective at preventing premature ovulation during OS treatment, and the incidence of developing embryo and pregnancy outcomes in patients using MPA were similar to those in patients using GnRH antagonists. Therefore, the use of MPA instead of GnRH antagonists during OS may be a viable alternative for patients not scheduled for fresh ET.

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(1) Background: Controversial conclusions have been made in previous studies regarding the influence of autologous platelet-rich plasma (PRP) in the reproductive outcomes of women with repeated implantation failures (RIF) who are undergoing embryo transfer (ET). (2) Methods: This study aimed to evaluate the effect of PRP intrauterine infusion in patients with unexplained RIF, who are undergoing in vitro fertilization (IVF) or intracytoplasmic injection (ICSI), by a systematic review and meta-analysis. (3) Results: A fixed-effects model was used, and 795 cases and 834 controls were included in these studies. The pooling of the results showed the beneficial effect of PRP which were compared with those of the control in terms of the clinical pregnancy rates (n = 10, risk ratio (RR) = 1.79, 95% confidence intervals (CI): 1.55, 2.06; p < 0.01, I2 = 40%), live birth rates (n = 4, RR = 2.92, 95% CI: 2.22, 3.85; p < 0.01, I2 = 83%), implantation rates (n = 3, RR = 1.74, 95% CI: 1.34, 2.26; p < 0.01, I2 = 0%), and positive serum ß-HCG 14 days after the ET (n = 8, RR = 1.77, 95% CI: 1.54, 2.03; p < 0.01, I2 = 36%). However, we did not find that the miscarriage rates indicated a significant difference between the two groups (n = 6, RR = 1.04, 95% CI: 0.72, 1.51; p = 0.83, I2 = 0%). (4) Conclusions: The findings of this systemic review and meta-analysis suggest that PRP appears to improve the results of IVF/ICSI treatments in the cases of unexplained RIF.

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OBJECTIVE: This study aimed to determine whether or not developmental potential impacts clinical outcomes, when good grade blastocysts from Days 5 and 6 were transferred in frozen embryo transfer (FET) cycles. METHODS: 654 women, including 460 (70.33%) on Day 5 and 194 (29.66%) on Day 6 were analyzed, in which 905 Day-5 and 274 Day-6 blastocysts were transferred. Only grade AA, AB, BA, BB quality and expansion grade between 3-6 (Gardner grading system) blastocysts survived and were included. RESULTS: The implantation rate was higher, 41.9% (379/905) in normal Day-5 compared to delayed Day-6 blastocyst transfers - 36.5% (100/274), but not significant (p=0.1). The clinical pregnancy rate was similar and not significant (p=0.4) in normal Day-5 (32.4%), compared to delayed Day-6 (35%). Miscarriage rates were higher in normal Day-5 (13.3%) compared to delayed Day-6 (6.3%) blastocyst transfers but were not significant (p=0.06). On the other hand, the biochemical pregnancy rate was significantly higher (p=0.001) in the delayed Day-6 blastocysts (16.7%) transfer group compared to patients with normal Day-5 (2.4%) blastocyst transfers. Two patients had ectopic pregnancies from the delayed Day-6 blastocyst transfer group. Live-Birth rates were significantly higher in Day-5 blastocysts compared to Day-6 (p=0.03). CONCLUSIONS: The developmental potential of embryos should not be considered a negative influence on pregnancy outcomes, especially good grade blastocysts vitrified on Days 5 and 6. Fully expanded blastocysts on Day-5 are considered similar in terms of outcomes to delayed Day-6 blastocysts; however, live-birth rates are significantly higher in Day-5 blastocysts.

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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.

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OBJECTIVE: To investigate whether the cumulative clinical pregnancy rates (CCPR) and cumulative live birth rates (CLBR) increase as the oocyte retrieval cycle increases in women with poor ovarian response. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENTS: Women diagnosed of poor ovarian response (POR) according to the Bologna criteria and who completed in vitro fertilization or intracytoplasmic sperm injection cycles between January 2014 and December 2018. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The conservative and optimistic estimations of CCPR and CLBR. RESULTS: The conservative and optimistic estimates of CCPR peaked at the 6th complete cycle, reaching 36.44% and 71.61%, respectively. However, the conservative and optimistic estimates of CLBR peaked at the 4th complete cycle, reaching 20.22% and 38.31%, respectively. The live birth rate per complete cycle of mild stimulation protocol was comparable to other protocols after adjusting for the confounding factors. For patients ≤35 years, the live birth rate per complete cycle of progestin-primed ovarian stimulation (adjusted odds ratio = 0.51, 95% confidence interval: 0.30-0.87) and gonadotropin-releasing hormone antagonist protocol (adjusted odds ratio=0.45, 95% confidence interval: 0.24-0.81) were significantly lower than that of the mild stimulation. CONCLUSIONS: It is not advisable to initiate more than four complete cycles for POR patients since CLBR do not increase after that. For POR patients ≤35 years, the live birth rate per complete cycle increased in women with mild stimulation protocol.

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BACKGROUND: Women with irregular menstruation should be considered to benefit from the ovarian stimulation. However, most literature did not separate ovulatory disorders from normal menstrual cycles. Our purpose was to assess the superiority of ovarian mild stimulation compared with the natural cycle in IUI for subfertile couples when the women with regular menstruation. METHODS: A retrospective study in a single medical center in which 2413 couples with 3573 IUI cycles were studied from 2013 to 2018. The results of IUI in natural cycles versus low-dose HMG induced cycles were analyzed. RESULTS: For young women (age < 35 years) with normal menstrual cycle, HMG induced ovulation combined with IUI can improve clinical pregnancy outcome (13.55% in two follicular induced cycles vs. 7.23% in natural cycles, p < 0.01); even if only one follicle was induced, the clinical pregnancy rate was increased to 10.32% (p < 0.01). When two growth follicles were induced in HMG cycles, a remarkable improvement of the live birthrate (10.28% vs. 5.91% in natural cycles, p < 0.05) was noted. Simultaneously, twin pregnancy rates were increased to 20.69% (p < 0.01). Twin pregnancies showed significantly increased risk of both ectopic pregnancy and preterm birth (p = 0.00 for both). For advanced women (age ≥ 35 years) with regular menstrual cycle, ovulation induction didn't improve clinical pregnancy and live birthrates, while age was the only relevant factor. CONCLUSIONS: Combining HMG induced ovulation and IUI can improve pregnancy outcome in young women with normal menstrual cycles. 1-2 follicles with diameter ≥ 14 mm served as the purpose of ovulation induction. Further, both twin and ectopic pregnancy rate in HMG cycles with two growth follicles were significantly higher than those in natural cycles were. Therefore, doctors must evaluate the risk before making choices and inform the patients to achieve the best results. For advanced women with normal menstrual cycles, natural IUI cycles were optional.

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Introduction For patients considering undergoing assisted reproductive techniques (ART), many concerns arise when persistent ovarian cysts are found. This large study aimed to determine how ovarian cyst removal affects success rates of IVF/ICSI therapies. Methods 550 patients who underwent an IVF/ICSI treatment between 2002 and 2011 with a persistent ovarian cyst ≤ 5 cm before treatment were analyzed retrospectively. 328 patients' preference was to undergo a laparoscopic cystectomy and 222 patients opted for a conservative management. Control subjects included 13 552 patients undergoing IVF/ICSI at the same period of time without an ovarian cyst. Results After adjusting for age, patients with ovarian cysts without surgery needed a significant higher stimulation dose than the control group (2576.4 vs. 2207.5 IU, p < 0.001). However, on average, they had 1.13 (- 0.25 - 2.01) higher oocyte number retrieved compared to the operated patients (9.0 ± 5.5 vs. 8.2 ± 5.0) (p = 0.012). Patients after surgical cyst removal had a significant lower number of oocytes retrieved (MNOR) in comparison to the control group (8.2 ± 5.0 vs. 9.5 ± 5.4) (p = 0.00). Compared to controls, operated patients had similar clinical pregnancy rate (CPR) (34.2 vs. 33.5%) OR 1.031 (95% CI 0.817 - 1.302) (p = 0.815). Compared to controls, patients without surgery showed significant lower pregnancy rate (34.2 vs. 25,7%) OR 1.428 (95% CI 1.054 - 1.936) (p = 0.002) and lower live birth rate (LBR) (21.9 vs. 13.5%) OR 1.685 (95% CI 1.143 - 2.485) (p = 0.008). Conclusions Ovarian cystectomy did not negatively impact the pregnancy rate or the live birth rate compared to controls.

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OBJECTIVE: To investigate whether serum levels of estradiol affect reproductive outcomes of normoresponder women undergoing fresh embryo transfer (ET) versus frozen-thawed ET (FET). MATERIAL AND METHODS: Two hundred fifty-five normoresponder women underwent fresh ET in their first or second in vitro fertilization cycle. Ninety-two women with negative pregnacy test results underwent FET. Clinical and ongoing pregnancy rates, implantation, and live birth rates of women undergoing fresh ET versus FET were compared. RESULTS: One hundred forty-seven (57.65%) out of the 255 normoresponder women receiving FET had positive beta-human chorionic gonadotrophin (hCG) results. The remaining 108 women had negative beta-hCG results. The clinical pregnancy rates of the fresh ET group were found as 55.69% (n=142). Ninety-two of the 108 women with failed pregnancies underwent FET; 72.83% had positive beta-hCG results (n=67), and 70.65% had clinical pregnancy (n=65). Both biochemical and clinical pregnancy rates of women undergoing FET increased significantly (p<0.012 and p<0.013, respectively). Ongoing pregnancy (60.87% vs. 52.94%) and live birth rates (59.87% vs. 48.63%) were similar in both fresh and FET groups. Serum E2 levels of women who failed to conceive were significantly higher than those women did conceive. Serum progesterone levels of women who conceived versus those that did not were similar. CONCLUSION: The detrimental effect of high serum estradiol levels on endometrial receptivity could be prevented by FET.

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OBJECTIVE: In 1991, researchers reported that a modest preovulatory increase in serum progesterone levels is associated with lower pregnancy rates and higher incidence of pregnancy loss in in vitro fertilization (IVF). We wonder whether embryo transfer (ET) in assisted reproductive technology (ART) cycles in patients with premature progesterone rise (PPR) have a negative impact on the clinical pregnancy rates (CPRs) and/or live birth rates (LBRs) in our series. Consequently, will blastocyst transfer reverse the negative impact? MATERIALS AND METHODS: This noninterventional, retrospective, observational tertiary center study was conducted between January 2010 and December 2012. All fresh ET cycles with serum progesterone levels measured (n = 599) on the day of hCG administration were analyzed. RESULTS: Sera lutenizing hormone (LH), E2, and progesterone (P) were measured and analyzed. The CPRs of cycles in patients with p ≤ 1.5 ng/mL (low) versus those with p > 1.5 ng/mL (high) were 37.04% versus 41.03% [odds ratio (OR) = 1.18, 95% confidence interval (CI): 0.728-1.920; p = 0.50). The LBRs of cycles in patients with low progesterone level versus those with PPR were 30.52% versus 34.62% (OR = 1.21, 95% CI: 0.729-1.992; p = 0.47). No statistically significant association was detected. We further analyzed the outcomes according to different stages of ET and found that blastocyst (D5) ET significantly increase the LBRs as compared with cleavage stage (D2/D3) ET in the PPR group (44.44% versus 21.43%; p = 0.043). CONCLUSION: PPR did not significantly compromise the clinical outcomes in this series. However, shifting to blastocyst transfer probably could increase the live birth in cycles with PPR.

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OBJECTIVE: To evaluate the efficacy of blastocyst transfer in comparison with cleavage stage transfer. STUDY DESIGN: A randomized, prospective study was conducted in Infertility clinic, Department of Obstetrics and Gynecology, Mahatma Gandhi Hospital, Jaipur on 300 patients aged 25-40 years undergoing in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycle from May 2010-April 2011. When three or more Grade-I embryos were observed on day 2 of culture, patients were divided randomly into two study groups, cleavage stage transfer and blastocyst transfer group having 150 patients each. Primary outcomes evaluated were, Clinical pregnancy rate and Implantation rate. The results were analyzed using proportions, standard deviation and Chi-square test. RESULTS: Both the groups were similar for age, indication and number of embryos transferred. Clinical pregnancies after blastocyst transfer were significantly higher 66 (44.0%) compared to cleavage stage embryo transfer 44 (29.33%) (P < 0.01). Implantation rate for blastocyst transfer group was also significantly higher (P < 0.001). CONCLUSION: Blastocyst transfer having higher implantation rate and clinical pregnancy rate lead to reduction in multiple pregnancies.

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OBJECTIVE: To investigate the impact of meiotic spindle normality on live birth rates in women with recurrent IVF failure. DESIGN: A retrospective comparative study. SETTING: A large private sector IVF service in Sydney, Australia. PATIENT(S): Five hundred five intracytoplasmic sperm injection (ICSI)/ET cycles of patients who fulfilled the criteria for recurrent IVF failure, three or more previous fresh or frozen ETs with no ongoing pregnancy. INTERVENTION(S): Polarized light microscopy was used at the time of ICSI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates (PR) and live birth rates (LBR) were compared depending on the morphology of the meiotic spindle of the oocyte(s) from which the embryo(s) were transferred. RESULT(S): Women receiving embryos where at least one was derived from a normally spindled oocyte had significantly increased clinical PR and LBR when compared with those who had only embryos derived from abnormally spindled oocytes (clinical PR: 31% vs. 7%; odds ratio [OR], 6.45; 95% confidence interval [CI] 3.65-11.40) and (LBR: 24% vs. 4%; OR, 7.24; 95% CI 3.62-14.49). Comparison between the abnormal spindle groups showed significantly higher clinical PR and LBR from the group of patients receiving embryos where at least one was derived from an oocyte with no visible spindle compared with the group receiving embryos from dysmorphic spindles only (clinical PR: 9% vs. 6%; OR, 0.58; 95% CI 0.22-1.57 and LBR: 8% vs. 1%; OR, 0.16; 95% CI 0.03-0.77). CONCLUSION(S): Normally spindled oocytes, as determined by polarized light microscopy, are associated with significantly higher clinical PRs in patients with recurrent IVF failure.

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