Pregnancy Outcomes of the First Thawing Cycle in “Freeze-All” Strategy of Infertility Patients with Fever During Oocyte Recruitment: A Matched-Pair Study
Infertility is a significant medical and social issue affecting millions of couples worldwide. Assisted reproductive technology (ART) has become a cornerstone in addressing infertility, with in vitro fertilization (IVF) being one of the most effective methods. However, the process of IVF is complex and involves multiple steps, each of which must be carefully managed to ensure success. One critical step in IVF is oocyte retrieval, which is typically performed under transvaginal ultrasound guidance. While this procedure is generally safe and minimally invasive, certain complications can arise, particularly in patients who develop a fever during the oocyte recruitment phase.
The impact of fever on oocyte retrieval and subsequent pregnancy outcomes has not been extensively studied. Fever can potentially increase the risk of pelvic infections, affect endometrial receptivity, and compromise embryo quality, all of which could lead to poor pregnancy outcomes. This study aimed to investigate the pregnancy outcomes of infertility patients who experienced fever during oocyte retrieval and subsequently underwent a “freeze-all” strategy, where all embryos were cryopreserved for later transfer.
The study was designed as a 1:3 retrospective matched-pair analysis, comparing 58 infertility patients who had a fever during oocyte retrieval (Group 1) with 174 age-matched controls who underwent whole embryo freezing for other reasons (Group 2). The primary objective was to evaluate the safety and efficacy of oocyte retrieval in febrile patients and to assess the impact of fever on embryo quality and pregnancy outcomes.
All patients in the study underwent standard controlled ovarian stimulation (COS) protocols, including the use of gonadotropin-releasing hormone (GnRH) agonists or antagonists, human menopausal gonadotropin (hMG), and recombinant human chorionic gonadotropin (rhCG) for oocyte maturation. Oocyte retrieval was performed 36 to 38 hours after rhCG administration. Patients in Group 1 had a fever (≥37.3°C) within 72 hours before oocyte retrieval, with the majority (91.4%) experiencing upper respiratory tract infections. All patients received oral antibiotics for three days post-retrieval to prevent pelvic infections.
The baseline characteristics of the patients were comparable, with no significant differences in age, body mass index (BMI), basal follicle-stimulating hormone (FSH), basal luteinizing hormone (LH), basal estradiol (E2), or infertility type (primary or secondary). However, the anti-Mullerian hormone (AMH) levels were significantly higher in Group 2 (4.2 ng/mL vs. 2.2 ng/mL, P<0.001), and the duration of infertility was longer in Group 2 (3 years vs. 2 years, P=0.035).
In terms of ovarian stimulation outcomes, there were no significant differences in the stimulation protocols, total gonadotropin (Gn) dosage, or intracytoplasmic sperm injection (ICSI) rates between the two groups. However, the number of oocytes retrieved was significantly lower in Group 1 (10.9±4.6 vs. 17.4±5.9, P<0.001), and the fertilization rate was also lower (81.0% vs. 90.6%, P<0.001). Interestingly, the two pronucleate (2PN) rate was higher in Group 1 (66.7% vs. 57.4%, P<0.001), but the number of available embryos (both day 3 and day 5) was similar between the groups.
The pregnancy outcomes of the first frozen-thawed embryo transfer (FET) cycle were then analyzed. There were no significant differences in endometrial thickness, the number of embryos transferred, or the type of luteal support supplementation between the two groups. The implantation rate (36.4% vs. 40.2%), clinical pregnancy rate (48.3% vs. 52.0%), early spontaneous abortion rate (17.9% vs. 13.3%), ectopic pregnancy rate (3.6% vs. 1.1%), and ongoing pregnancy rate (37.9% vs. 44.5%) were all comparable, with no statistically significant differences.
To account for potential confounding variables, binary logistic regression analysis was performed. The results showed that the clinical pregnancy rate and ongoing pregnancy rate were not significantly different between the two groups after adjusting for age, BMI, AMH levels, the number of embryos transferred, and endometrial thickness. Additionally, when patients were stratified based on the severity of fever (T < 38°C vs. T ≥ 38°C), there were no significant differences in clinical pregnancy rate or ongoing pregnancy rate.
The findings of this study suggest that transvaginal ultrasound-guided oocyte retrieval is a safe and minimally invasive procedure for infertility patients who develop a fever during the oocyte recruitment phase. The use of a “freeze-all” strategy, where all embryos are cryopreserved and transferred in a subsequent FET cycle, appears to be an effective approach for these patients. This strategy not only minimizes the risk of pelvic infections but also allows for embryo transfer in a more receptive endometrial environment, potentially improving pregnancy outcomes.
The study also highlights the importance of AMH as a sensitive marker of ovarian function, as it was significantly higher in the control group, which had a higher number of oocytes retrieved. Fever did not appear to affect the rate of embryo formation, as the number of available embryos was similar between the two groups. This suggests that while fever may impact the number of oocytes retrieved and the fertilization rate, it does not compromise the quality of the embryos formed.
In conclusion, this study provides valuable insights into the management of infertility patients who develop a fever during oocyte retrieval. The findings support the use of a “freeze-all” strategy, where all embryos are cryopreserved and transferred in a subsequent FET cycle, as a safe and effective approach for these patients. This strategy not only minimizes the risk of complications but also optimizes the chances of achieving a successful pregnancy. Further research with larger sample sizes and randomized controlled trials is needed to confirm these findings and to explore the underlying mechanisms by which fever may impact oocyte retrieval and embryo quality.
doi.org/10.1097/CM9.0000000000001238
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