Objective: To investigate the effects of body mass index (BMI) on assisted reproductive outcomes with the freeze-all strategy for patients with polycystic ovary syndrome (PCOS). Design: Retrospective cohort study. Setting: Tertiary care academic medical center. Patient(s): A total of 3,079 women with PCOS across different BMIs at our institution from January 2015 to May 2017 were stratified into cohorts. Intervention(s): None. Main Outcome Measure(s): Implantation rate, clinical pregnancy rate, early miscarriage rate, and live birth rate. Result(s): The live birth rate was most favorable in underweight (BMI < 18.5 kg/m 2 ) and normal weight cohorts (18.5 % BMI < 25 kg/ m 2 ) and progressively decreased as BMI increased. Moreover, the obese cohort (BMI R 30 kg/m 2 ) of patients with PCOS who had frozen ET cycles had a relatively high early miscarriage rate. Conclusion(s):The live birth rates are highest in underweight and normal weight patients with PCOS undergoing IVF with the freeze-all strategy. Furthermore, there is a progressive and statistically significant decrease in the live birth rate and an increase in the miscarriage rate in obese patients with PCOS. (Fertil Steril Ò 2019;112:1172-9. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
Purpose: To investigate whether progestin-primed ovarian stimulation (PPOS) can be an alternative as gonadotrophin-releasing hormone agonist (GnRHa) long protocol for infertile women with normal ovarian reserve during IVF/ICSI. Methods: A prospective randomized controlled trial (RCT) including 257 patients was conducted between 1 August 2017 to 1 January 2018. Computerized randomization was performed to assign participants into two treatment groups at a 1:1 ratio: PPOS (130 patients) or GnRHa long protocol (127 patients) followed by their first IVF/ICSI with fresh/frozen embryo transfer. The primary outcome was the number of oocytes retrieved. Patients with normal ovarian reserve undergoing their first IVF/ICSI procedure were included. The embryological and clinical outcomes were measured. Only the first embryo transfer cycle was followed-up. Results: Basic characteristics such as infertility duration, age, and body mass index (BMI) were comparable in both groups. No significant difference was found in the number (mean ± SD) oocytes retrieved [11.8 ± 6.5 for PPOS vs 11.3 ± 5.6 for GnRHa long protocol] or viable embryos [4.5 ± 3.0 for PPOS vs 4.2 ± 2.9 for GnRHa long protocol] between the groups. No patient from either group experienced a premature LH surge during the whole process of ovarian stimulation. Besides, there was no moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation in PPOS group while three patients suffered it in the GnRHa long protocol group. There was no significant difference in the clinical pregnancy rate of the first embryos transfer cycle between the two groups. Conclusion: PPOS in combination with embryo cryopreservation as an ovarian stimulation regimen was as effective as GnRHa long protocol during controlled ovarian stimulation (COH) under different endocrinal mechanisms. It can also achieve comparable embryological and clinical outcomes while reducing the incidence of moderate and severe ovarian hyperstimulation syndrome (OHSS) and HMG dosage. It can be an alternative of the treatments for infertile patients with normal ovarian reserve undergoing IVF as well as traditional protocols.
Background: Endometrial preparation is essential in frozen-thawed embryo transfer (FET) cycles. Recent studies suggested that different endometrial preparation methods may influence obstetrical complications. However, the association between hormone replacement therapy (HRT) and ovarian stimulation (OS) FET endometrial preparation and obstetrical complications remains unknown.Methods: This retrospective cohort study included a total of 79,662 confirmed embryo transfer cycles during the period from January 2003 to December 2019. After exclusion, the remaining cases were categorized into an ovarian stimulation FET group (OS FET group, n = 29,121) and a hormone replacement therapy FET group (HRT FET group, n = 26,776) and subjected to the analyses. The primary outcome was the rate of obstetrical complications included placenta previa, placenta abruption, hypertensive disorders of pregnancy (HDP), placenta accreta, gestational diabetes mellitus (GDM), preterm premature rupture of the membrane (pPROM). The secondary outcome was pregnancy outcomes such as live birth rate, birth weight, pre-term and post-term delivery and cesarean sections. In order to minimize the bias, 10 pregnancy-related factors were adjusted in multiple logistic regression analysis.Results: Placenta previa (0.6 vs. 1.2%, P < 0.001) and HDP (3.5 vs. 5.3%, P < 0.001) were found lower in the OS FET than HRT FET group. Cesarean section was observed lower in the OS than HRT group (76.3 vs. 84.3%, P < 0.001). After adjustment for 10 important pregnancy-related confounding factors, we found that the risk of placenta previa (aOR 0.54, 95% CI 0.39–0.73) and HDP (aOR 0.65, 95% CI 0.57–0.75) and cesarean section (aOR 0.61, 95% CI 0.57–0.66) were still significantly reduced in the OS than HRT group. Furthermore, live birth rates were higher (80.0 vs. 76.0%, P < 0.001), and the miscarriage rate was lower (17.7 vs. 21.3%, P < 0.001) for pregnancies conceived with OS FET than with HRT FET. And the average birth weight was lower in the OS group compared to HRT group (2982.3 ± 636.4 vs. 3025.0 ± 659.0, P < 0.001), as well as the small-for-gestational age (SGA) was higher (8.7 vs. 7.2%, P < 0.001) and the large-for-gestational age (LGA) was lower (7.2 vs. 8.6%, P < 0.001) in the OS group than in the HRT group.Conclusions: The risks of placenta previa and HDP were lower in patients conceiving after OS FET than in those after HRT FET. Further prospective studies are required to further clarify the mechanism underlying the association between endometrium preparation and obstetrical complications.
Background: Previous studies have reported the association between embryo quality and perinatal outcomes in fresh cycles, after cleavage-stage or blastocyst embryo transfer, and found no significant difference. However, in terms of vitrified-warmed embryo transfer cycles, the impact of embryo quality on neonatal and maternal outcomes has not been evaluated.Objectives: To explore the association between the quality of a single vitrified-warmed embryo and perinatal outcomes.Methods: This retrospective study included 2403 live-born singletons derived from single vitrified-warmed embryo transfer cycles during January 2006 and July 2018. Neonatal and maternal outcomes were compared between singletons resulting from the use of single good quality embryo (GQE) (n = 1854) and single poor quality embryo (PQE) (n = 549) and analyzed in the group of cleavage-stage embryo transfer and the group of blastocyst transfer, respectively.Results: A significantly higher risk of low birthweight (LBW, birthweight <2500 g) was observed in the singletons derived from the transfer of single PQE compared with those derived from the transfer of single GQE both in cleavage and blastocyst stages (cleavage-stage, AOR 2.62, 95% CI 1.27-5.37; blastocyst stage, AOR 1.98, 95% CI 1. 06-3.70). An increased risk of preterm birth (PTB, gestational age <37 weeks) was also observed in singletons born after transfer of a PQE of cleavage-stage compared with those after a GQE of cleavage-stage (AOR 2.40, 95% CI 1.28-4.49). The transfer of single poor quality blastocyst was associated with a higher risk of placenta previa compared with the transfer of single good quality blastocyst (AOR 2.65, 95% CI 1.26-5.57). Other maternal complications, neonatal malformations, and neonatal complications were similar between compared groups. Conclusion:In vitrified-warmed cycles with single embryo transfer, poor embryo quality would result in a significantly higher risk of LBW, regardless of cleavage-stage or blastocyst embryo transfer. Meanwhile, the transfer of poor cleavage-stage embryo was also associated with an increased incidence of PTB.
IntroductionWomen with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) protocols are typically characterised by an increased number of oocytes retrieved. The oocytes are often of poor quality, leading to lower pregnancy rates, higher miscarriage rates and an increased risk of developing ovarian hyperstimulation syndrome (OHSS). Since our previous preliminary study showed that a novel progestin-primed ovarian stimulation (PPOS) protocol blocked the luteinising hormone (LH) surge during IVF and achieved a higher pregnancy rate with a lower incidence of OHSS, we designed a prospective randomised controlled trial to compare the efficacy and safety of this PPOS protocol with the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS who are undergoing IVF procedures.Methods and analysisPatients with PCOS will be randomised to one of two controlled ovarian stimulation regimens—GnRH antagonist or PPOS—using a computer-generated random number. A freeze-all strategy using embryo vitrification techniques and frozen embryo transfer will be performed in both groups. The primary outcome is the live-birth rate per transfer. Secondary outcomes include the incidence of premature LH surges, the duration and total dose of human menopausal gonadotropin stimulation, the number of oocytes retrieved, the incidence of moderate or severe OHSS, the number of embryos available for transfer, implantation rates, clinical pregnancy rates, pregnancy loss rates, ectopic pregnancy rates, pregnancy and neonatal complications, and congenital anomalies. The necessary sample size for this trial was estimated as 392 participants, with 196 participants in each group. Intention-to-treat analysis was used in processing our experimental data.Ethics and disseminationThis study was approved by the Institutional Review Board of the hospital (2016-133-T82). The trial will be conducted according to the principles of the World Medical Association’s Declaration of Helsinki and in accordance with Good Clinical Practice standards. The findings of this trial will be published in a peer-reviewed journal.Trial registration numberChiCTRIPR16009580.
Purpose: To investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT). Patients and Methods: This retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded. Results: Baseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.3% vs 36.1%). After adjustment for 12 pregnancy-related confounding factors, logistic regression analysis showed that LBR remained significantly higher in the scHRT-FET group than in the HRT-FET group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.14-1.49). Furthermore, after adjustment, the ongoing pregnancy rate was significantly higher (aOR 1.29, 95% CI 1.13-1.47), and the miscarriage rate was significantly lower (aOR 0.58, 95% CI 0.43-0.77), in the scHRT-FET group compared to the HRT-FET group. Adjuvant vaginal use of SC did not increase the endometrial thickness and had no significant effect on birth weight or PTB. Conclusion: Adjuvant vaginal use of SC in HRT FET was associated with higher LBR and improved pregnancy outcomes in an infertile population with adequate endometrial thickness. The beneficial effect of SC may be due not to an increase in EMT but instead to improve endometrial blood flow and receptivity, which might merit clinicians' attention for improving general IVF practices.
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