BackgroundWith the widespread application of assisted reproduction technology (ART) and increased pelvic inflammatory disease, the incidence of heterotopic pregnancy (HP) has risen. However, the risk factors and treatment of HP remain indefinite.ObjectivesTo explore risk factors affecting the incidence of HP secondary to in vitro fertilization-embryo transfer (IVF-ET) and pregnancy outcomes after surgical treatment of HP.Methods29 patients with HP and 116 with an intrauterine-only pregnancy (IUP) after IVF-ET during the same period were included retrospectively from January 2015 to September 2020.ResultsPatients with HP had a higher proportion of previous ectopic pregnancies, multiple abortion history (≧2 times) and tubal indication for IVF than IUP. Besides, they had a greater possibility to end in spontaneous abortion (31.03 vs.13.79%, P = 0.028) and preterm delivery (25.00 vs. 7.00%, P = 0.035), less possibility to result in a live birth (58.62 vs. 78.45%, P = 0.028). History of multiple abortions (≥2 times) [odds ratio (OR) 3.031, 95% confidence intervals (CI) 1.087–8.453; P = 0.034], tubal infertility (OR 3.844, 95% CI 1.268–11.656; P = 0.017), previous ectopic pregnancies (OR 2.303, 95% CI 0.625–8.490; P = 0.021) and number of embryo transfer (OR 0.300, 95% CI 0.092–0.983; P = 0.037) resulted in an elevated proportion of HP in IVF treatment. Shorter operative duration, smaller size of the ectopic mass and location in the ampulla of the fallopian tube were associated with higher chance of survival in the coexistent intrauterine pregnancy after surgical treatment.ConclusionsPrevious history of ectopic pregnancy, multiple abortions, tubal infertility and multiple-embryo transfer may be considered as meaningful risk factors of subsequent HP following IVF-ET. In patients with HP treated by surgery, shorter operative duration, smaller size of the ectopic mass and location in the ampulla of the fallopian tube means better reproductive prognosis.

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Background There is still no consensus on the optimal time of oocyte–sperm co-incubation during in vitro fertilization and embryo transfer (IVF-ET). The aim of this meta-analysis was to compare the effects of brief (1-6 h) and long (16-24 h) gametes co-incubation time on IVF outcomes. Methods The study protocol was registered online through PROSPERO (CRD42022337503) and PRISMA guidelines were followed in the present study. The following databases were searched from inception to May 2022 for randomized controlled trials (RCTs): PubMed, Embase, Cochrane library, Web of Science, using search terms related to IVF, gametes, time of co-incubation and reproductive outcome measure. Studies comparing outcomes of brief co-incubation to that of long co-incubation during IVF, and reporting primary outcome (live birth rate), secondary outcomes (clinical pregnancy rate; ongoing pregnancy rate; miscarriage rate; normal fertilization rate; polyspermy rate; top-quality embryo rate; implantation rate) were searched. A total of 11 studies were included in the meta-analysis. Combined odds ratio (OR) and 95% confidence interval (CI) were calculated for the data. Statistical heterogeneity analysis between studies was assessed by Cochran Q and I2 statistic with a significant threshold of P < 0.05. Methodologic quality assessment of RCTs was made for potential risk of bias with Cochrane Risk of Bias Tool. Results Compared to long-term co-incubation, brief co-incubation had an advantage in increasing implantation rate (OR: 1.97, 95% CI: 1.52–2.57), ongoing pregnancy rate (OR: 2.18, 95% CI: 1.44–3.29) and top-quality embryo rate (OR: 1.17, 95% CI: 1.02–1.35). However, brief co-incubation of gametes had no advantages in the live-birth rate (OR: 1.09, 95% CI: 0.72–1.65), miscarriage rate (OR: 1.32, 95% CI: 0.55–3.18), clinical pregnancy rate (OR: 1.36, 95% CI: 0.99–1.87) and polyspermy rate (OR: 0.80, 95% CI: 0.48–1.33) than long-term co-incubation. Additionally, the brief co-incubation was associated with lower normal fertilization rate (OR: 0.89, 95% CI: 0.80–0.99), compared with long co-incubation. Conclusions Brief co-incubation of gametes had the advantages in increasing implantation rate, ongoing pregnancy rate and top-quality embryo rate than long-term co-incubation. However, the live-birth rate displayed no difference between the two in vitro fertilization methods. Gametes co-incubation time should be individualized according to each patient’s IVF history, infertility causes and the semen parameters.

We conducted a systematic review and meta-analysis of all published data to determine the impact of estradiol pretreatment on reproductive outcomes and ovary stimulation characteristics for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with gonadotropin-releasing hormone (GnRH) antagonist protocol. MEDLINE, EMBASE, Cochrane Library, Web of Science, and China National Knowledge Infrastructure were searched, and any randomized controlled trials associated with estradiol pretreatment in GnRH antagonist protocol were included. Seven studies (1,236 patients) were included in the present study. The pooled data from the meta-analysis demonstrated no significant difference in ongoing pregnancy rate (odds ratio (OR): 0.92 (95% CI: 0.69–1.21; P = 0.53) and live birth rate OR: 0.98 (95% CI: 0.74–1.30; P = 0.90) between patients with and those without estradiol pretreatment in GnRH antagonist protocol. Duration of gonadotropin exposure, gonadotropin consumption, and the number of cumulus–oocyte complexes were not significantly different between groups. Luteal estradiol pretreatment in IVF/ICSI cycles with GnRH antagonist protocol in normal ovary responding population does not affect the reproductive outcomes. It is an encouraging option to facilitate cycle scheduling in GnRH antagonist protocol, for luteal estradiol pretreatment does not increase the duration of gonadotropin exposure or gonadotropin consumption.