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Background: Embryo quality may affect birth weight among neonates born through assisted reproductive technology. There are very limited studies assessing the adverse effect of transferring a poor-quality embryo with a good-quality one on neonatal outcomes. Objective: The aim of this study was to evaluate the effect of double embryo transfer (DET) with one good-quality embryo (GQE) plus a poor-quality one on the birth weight of newborns conceived by in vitro fertilization in both fresh and frozen-thawed embryo transfer cycles. Materials and Methods: This study was conducted at Yazd Reproductive Sciences Institute, Yazd, Iran. A total of 626 women were classified into three groups according to the embryo quality: single embryo transfer with a GQE (group A); DET using two GQEs (group B); and DET using one good-quality and one poor-quality embryo (group C). The primary outcome was singleton birth weight which was compared between the three groups among fresh and frozen-embryo transfer cycles. A comparative analysis was also performed regarding the effect of vitrification procedures on neonatal birth weight within each of the three embryo quality-based groups. Results: The mean birth weight and the rate of preterm birth were similar between the three groups (p = 0.45 and 0.32, respectively). There were also no significant differences found in the vitrification comparative analysis between and within the groups with regard to birth weight. Conclusion: Our results showed that a poor-quality embryo did not have a significant influence on a good-quality one regarding neonatal birth weight when transferred together. Key words: Embryo quality, Birth weight, Frozen-embryo transfer, Fresh embryo transfer, Single embryo transfer, Double embryo transfer.

To evaluate the effects of the addition of single-dose GnRH agonist to the routine progestogens use for luteal phase support on IVF outcome as compared to progestogens only. This is a retrospective case-control study on selected patients who underwent IVF treatment with fresh embryo transfer (ET) under Medically Assisted Conception Unit, University Kebangsaan Malaysia Medical Center for the period of June 2015-June 2018. A higher dose of 0.2 mg subcutaneous Decapeptyl was administered 2 days before fresh ET concurrent with routine progestogen support. Patients with different luteal phase regimes, frozen embryo transfer and medical records with missing data were excluded. Their medical records were reviewed, and data analyzed. The pregnancy outcomes measured included biochemical pregnancy rates, clinical pregnancy rates, live birth rates and miscarriage rates. A total of 786 patients were analyzed. Four hundred forty-four patients were given luteal phase support with progestogens and GnRH agonist, whereas 342 patients served as control were given progestogens only. The study group showed higher biochemical pregnancy rate (47.7 vs. 44.4%,), clinical pregnancy rate (25.7 vs. 23.4%) and livebirth rate (24.3 vs. 22.2%), respectively but not statistically significant. The rate of miscarriage among the study group was lower (4.5% vs 9.4%) compared to the progestogen group alone. Nonetheless, the OHSS rate was slightly increased in the study group (4.5 vs. 3.5%) despite using a mild stimulation protocol. New regime of GnRH agonist luteal support in addition to the standard progestogen support was found to be beneficial in overall IVF outcome.

Ovarian stimulation can cause supraphysiological estradiol levels and adverse effects on endometrial receptivity. Since patients could undergo cleavage or blastocyst stage embryo transfer, the threshold value of peak estradiol level for each transfer stage that impacts the pregnancy outcomes of fresh versus frozen embryo transfer remains unclear. This work aims at answering the following questions: what is the threshold of peak estradiol level that modifies the difference in pregnancy outcomes between fresh and frozen embryo transfer and whether the threshold value varies with the stage of embryo transferred? A secondary analysis of data from four multicenter randomized trials with similar design comparing the rate of live birth between fresh and frozen embryo transfer in a total of 6153 patients. Peak serum estradiol level was measured on the day of hCG administration. Live birth rate is the primary outcome. Multivariable regression modeling showed an interaction between the stage of embryo transferred and the intervention (frozen vs fresh embryo transfer) on the live birth rate (p = 0.016). In the cleavage-stage embryo transfer group, frozen embryo transfer resulted in a higher rate of live birth when peak estradiol level >3900 pg/mL (55.4% vs 44.9%; OR, 1.57; 95% CI, 1.24-1.99) and a similar live birth rate (OR, 1.10; 95% CI, 0.93-1.31) when peak estradiol level was 1600-3900 pg/mL. However, in the blastocyst transfer group, frozen embryo transfers yielded a higher live birth rate when peak estradiol level >2000 pg/mL (54.3% vs 37.7%; OR, 2.00; 95% CI, 1.59-2.51). A freeze-all strategy may result in a higher rate of live birth when the peak estradiol level >3900 pg/mL for cleavage-stage embryo transfer and when the peak estradiol level >2000 pg/mL for blastocyst transfer.

Background Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC). Methods We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups. Results Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60–1.80; I 2  = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20–1.50; I 2  = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00–6.51; I 2  = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58–1.92; I 2  = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33–1.53; I 2  = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively). Conclusions Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

Background Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients. Method The PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I 2 index were analyzed. Stata 15 was used for statistical analysis. Results A total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27–2.37, I 2  = 0.0%, n  = 410; frozen RR: 1.44, 95% CI: 1.14–1.81, I 2  = 0.0.%, n  = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33–2.23, I 2  = 0.0%, n  = 497; intrauterine RR: 1.39, 95% CI: 1.09–1.78, I 2  = 0.0%, n  = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28–2.68; I 2  = 20.1%, n  = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25–5.21: I 2  = 63.2%, n  = 472) and live birth rate (RR: 1.43, 95% CI: 0.86–2.36; I 2  = 52.5%; n  = 372) when a random-effects model was employed. Conclusion The administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.

The studies posits that there is not sufficient evidence to support the use of intrauterine platelet-rich plasma (PRP) infusion in patients with recurrent implantation failure (RIF). This study aims to investigate the effects of infusion of PRP on patients with unexplained-RIF in fresh and frozen embryo transfer (ET) cycles. A total of 80 participants were included in this study. The participants were randomly assigned to one of two groups with and without PRP infusion. Each of the PRP and control groups were also divided into fresh and frozen ET subgroups. ET outcomes were compared between groups. Clinical pregnancy rate was significantly higher in Frozen ET in PRP group than other subgroups ( p  < 0.0001). Miscarriage rate were significantly lower in PRP group than control group. Pregnancy complications and preterm labor were significantly higher in PRP group than control group ( p  < 0.0001). Live birth and healthy baby rate were significantly higher in PRP group than control group ( p  < 0.0001). The intrauterine infusion of 0.8-1 ml of PRP 48 h before blastocyst ET at fresh and frozen cycles can be an efficient treatment option for u-RIF patients. Also, results indicated that the clinical pregnancy rate was equal to the live birth rate at fresh ET cycles, whereas the live birth rate was lower than the clinical pregnancy rate at frozen ET cycles. Therefore, considering the superiority of fresh cycles over freeze cycles, the infusion of PRP into the uterus of patients with RIF is recommended to be done at fresh ET cycles. Trial registration : NCT, NCT03996837. Registered 25/06/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03996837.

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

PurposeThe use of assisted reproductive technology (ART) has increased in the last 2 decades and continuous surveillance is needed. This systematic review aims to assess the risk of adverse neonatal outcomes (preterm birth [PTB], low birth weight [LBW], small-for-gestationalage [SGA] and large for gestational-age [LGA]), in singleton pregnancies conceived by fresh or frozen embryo transfer (FET) compared to spontaneous conceptions.MethodsCohort studies were identified from MEDLINE, Embase, Cochrane Library (January 2019), and manual search. Meta-analyses were performed to estimate odds ratios (OR) using random effects models in RevMan 5.3 and I-squared (I2) test > 50% was considered as high heterogeneity.ResultsAfter 3142 titles and abstracts were screened, 1180 full-text articles were assessed, and 14 were eligible. For fresh embryo transfer, the pooled ORs were PTB 1.64 (95% CI 1.46, 1.84); I2 = 97%; LBW 1.67 (95% CI 1.52, 1.85); I2 = 94%; SGA 1.46 [95% CI 1.11, 1.92]; I2 = 99%, LGA 0.88 (95% CI 0.80, 0.87); I2 = 80%). For frozen, the pooled ORs were PTB 1.39 (95% CI 1.34, 1.44); I2 = 0%; LBW 1.38 (95% CI 0.91, 2.09); I2 = 98%; SGA 0.83 (95% CI 0.57, 1.19); I2 = 0%, LGA 1.57 (95% CI 1.48, 1.68); I2 = 22%).ConclusionsWhen compared with spontaneous pregnancies, fresh, but not frozen was associated with LBW and SGA. Both fresh and frozen were associated with PTB. Frozen was uniquely associated with LGA. Despite improvements in ART protocols in relation to pregnancy rates, attention is needed towards monitoring adverse neonatal outcomes in these pregnancies.

PurposeIn vitro maturation (IVM) is an alternative to in vitro fertilization (IVF) for women at high risk of developing ovarian hyperstimulation syndrome (OHSS). This study determined the effectiveness and safety of a freeze-only strategy versus fresh embryo transfer (ET) after IVM with a pre-maturation step (CAPA-IVM) in women with a high antral follicle count (AFC).MethodsThis randomized, controlled pilot study (NCT04297553) was conducted between March and November 2020. Forty women aged 18–37 years with a high AFC (≥24 follicles in both ovaries) undergoing one cycle of CAPA-IVM were randomized to a freeze-only strategy with subsequent frozen ET (n = 20) or to fresh ET (n = 20). The primary endpoint was ongoing pregnancy resulting in live birth after the first ET of the started treatment cycle.ResultsThe ongoing pregnancy rate in the freeze-only group (65%) was significantly higher than that in the fresh ET group (25%; p = 0.03), as was the live birth rate (60% versus 20%; p = 0.02). Clinical pregnancy rate was numerically, but not significantly, higher after frozen versus fresh ET (70% versus 35%; p = 0.06), while the number of day 3 or good quality embryos, endometrial thickness on the day of oocyte pick-up, implantation rate, and positive pregnancy test rate did not differ significantly between groups. No cases of OHSS were observed, and miscarriage and multiple pregnancy rates were similar in the two groups.ConclusionsThese findings suggest that the effectiveness of CAPA-IVM could be improved considerably by using a freeze-only strategy followed by frozen ET in subsequent cycles.Trial registration number:NCT04297553 (www.clinicaltrials.gov)

PurposeThe study aims to evaluate whether frozen embryo transfer can restore optimal receptivity leading to better assisted reproductive technology outcomes in women with endometriosis.MethodsThis systematic review and meta-analysis, conducted from January 10, 2021 to July 1, 2021, searched the Cochrane Library, PubMed, Embase, Web of Science, OVID, and Clinicaltrials.gov databases from inception to January 10, 2021. The search strategy combined search terms as follows: (“endometriosis” OR “deep endometriosis” OR “endometrioma”) AND (“frozen-thawed embryo transfer” OR “frozen embryo transfer” OR “freeze-all strategy”) AND (“pregnancy outcome” OR “live birth rate” OR “clinical pregnancy rate” OR “miscarriage rate”). No publication time or language limits were set during the searches. In addition, references of the related articles were searched by hand. Patients were included if they had a history of endometriosis and had received fresh or frozen embryo transfer. Only the first transfer cycle was included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to express outcomes, and data synthesis was conducted using RevMan, version 5.4 software.ResultsA total of six studies with moderate methodologic quality were retrieved in the meta-analysis. The studies included 3010 women with endometriosis who wanted to conceive; 1777 (59.0%) had frozen embryo transfer, and 1233 (41.0%) had fresh embryo transfer. There was a significantly higher frequency of live births in the frozen embryo group than in the fresh embryo group (OR, 1.53; 95% CI, 1.13–2.08; P = .007). Despite a similar clinical pregnancy rate in the two groups (OR, 1.26; 95% CI, 0.95–1.69; P = .11), the difference in miscarriage rate was significant (OR, 0.70; 95% CI, 0.50–0.97; P = .03). Evidence quality was considered moderate.ConclusionCryopreserved embryo transfer has resulted in preferable reproduction outcomes when compared with fresh embryo transfer in patients with endometriosis, but the evidence is not yet abundant. More strictly designed research is needed to evaluate whether frozen embryo transfer leads to better reproductive outcomes in women with endometriosis compared with those receiving fresh embryo transfer.Registration numberPROSPERO CRD42021248313.