Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Hum Reprod. 2021 May 17;36(6):1542-1551. doi: 10.1093/humrep/deab059.
Does unplanned spontaneous follicular growth and ovulation affect clinical outcomes after planned artificial frozen-thawed embryo transfer (AC-FET) cycles?
AC-FET and spontaneous follicular growth and ovulation events resulted in notably better pregnancy outcomes with a significantly higher implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and live birth rate (LBR) and a significantly lower miscarriage rate.
The AC-FET protocol without GnRH agonist administration is associated with a low incidence of follicular growth and ovulation. In the literature, authors often refer to these types of cycles with concern due to possibly impaired FET outcomes. However, the real impact of such cycles has yet to be elucidated due to the lack of existing data.
STUDY DESIGN, SIZE, DURATION: This was a retrospective clinical study involving 2256 AC-FET cycles conducted between January 2017 and August 2019. Propensity score (PS) matching was used to control for confounding variables.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects were divided into two groups: a study group: cycles with spontaneous follicular growth and ovulation (the maximum diameter of follicles in any ovary was ≥14 mm and ovulation was confirmed by consecutive ultrasound examinations) and a control group featuring cycles without growing follicles (the maximum diameter of follicles in both ovaries were <10 mm). The study group was matched by PS with the control group at a ratio of 1:2. The study group consisted of 195 patients before PS matching and 176 patients after matching. The numbers of participants in the control group before and after PS matching were 2061 and 329, respectively.
This analysis showed that patient age (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.09; P=0.010) and basal FSH level (aOR 1.06; 95% CI 1.01-1.11; P=0.012) were significantly and positively related with the spontaneous follicular growth and ovulation event. In addition, this event was negatively correlated with BMI (aOR 0.92; 95% CI 0.87-0.97; P=0.002), AMH level (aOR 0.66; 95% CI 0.59-0.74; P<0.001) and a high starting oestrogen dose (aOR 0.53; 95% CI 0.38-0.76 for 6 mg vs. 4 mg; P<0.001). Baseline characteristics were similar between groups after PS matching. Patients in the study group had a significantly higher IR (28.8% vs. 21.8%, P=0.016), CPR (44.9% vs. 33.4%, P=0.011), OPR (39.2% vs. 26.1%, P=0.002) and LBR (39.2% vs. 24.9%, P=0.001) and a lower miscarriage rate (12.7% vs. 25.5%, P=0.030), compared with those in the control group.
LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study carried out in a single centre and was therefore susceptible to bias. In addition, we only analysed patients with normal ovulation patterns and excluded those with follicular growth but without ovulation. Further studies remain necessary to confirm our results.
It is not necessary to cancel cycles that experience spontaneous follicular growth and ovulation. Our data support promising clinical outcomes after this event. Our findings are important as they can better inform clinicians and patients.
STUDY FUNDING/COMPETING INTEREST(S): This research was supported by National Natural Science Foundation of China (grant no. 81701507, 81801404, 81871210, 82071648), Natural Science Foundation of Jiangsu Province (grant no. BK20171126, BK20201123) and Jiangsu Province '333' project. The authors declare that they have no competing interests.
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计划外的自发卵泡生长和排卵是否会影响计划人工冻融胚胎移植（AC-FET）周期后的临床结局？
AC-FET 和自发卵泡生长和排卵事件导致显著更好的妊娠结局，具有显著更高的着床率（IR）、临床妊娠率（CPR）、持续妊娠率（OPR）和活产率（LBR），以及显著更低的流产率。
没有 GnRH 激动剂给药的 AC-FET 方案与卵泡生长和排卵的低发生率相关。在文献中，由于可能损害 FET 结局，作者经常对此类周期表示关注。然而，由于缺乏现有数据，这种周期的实际影响仍有待阐明。
研究设计、规模、持续时间：这是一项回顾性临床研究，涉及 2017 年 1 月至 2019 年 8 月期间进行的 2256 例 AC-FET 周期。使用倾向评分（PS）匹配来控制混杂变量。
参与者/材料、设置、方法：受试者分为两组：研究组：有自发卵泡生长和排卵的周期（任何卵巢的卵泡最大直径≥14mm，排卵通过连续超声检查证实）和无卵泡生长的对照组（两个卵巢的卵泡最大直径均<10mm）。研究组通过 PS 与对照组以 1:2 的比例匹配。PS 匹配前，研究组有 195 例患者，匹配后有 176 例患者。PS 匹配前后对照组的参与者人数分别为 2061 人和 329 人。
这项分析表明，患者年龄（调整后的优势比[aOR]1.05；95%CI 1.01-1.09；P=0.010）和基础 FSH 水平（aOR 1.06；95%CI 1.01-1.11；P=0.012）与自发卵泡生长和排卵事件显著正相关。此外，该事件与 BMI（aOR 0.92；95%CI 0.87-0.97；P=0.002）、AMH 水平（aOR 0.66；95%CI 0.59-0.74；P<0.001）和高起始雌激素剂量（aOR 0.53；95%CI 0.38-0.76，6mg 与 4mg 相比；P<0.001）呈负相关。PS 匹配后两组的基线特征相似。研究组的 IR（28.8%对 21.8%，P=0.016）、CPR（44.9%对 33.4%，P=0.011）、OPR（39.2%对 26.1%，P=0.002）和 LBR（39.2%对 24.9%，P=0.001）均显著更高，流产率（12.7%对 25.5%，P=0.030）更低。
局限性、谨慎原因：这是一项在单一中心进行的回顾性研究，因此易受偏倚影响。此外，我们只分析了具有正常排卵模式的患者，排除了有卵泡生长但无排卵的患者。进一步的研究仍然是必要的，以证实我们的结果。
不需要取消自发卵泡生长和排卵的周期。我们的数据支持在这一事件后的良好的临床结局。我们的发现很重要，因为它们可以更好地为临床医生和患者提供信息。
研究基金/利益冲突：本研究得到国家自然科学基金（项目编号：81701507、81801404、81871210、82071648）、江苏省自然科学基金（项目编号：BK20171126、BK20201123）和江苏省“333”项目的支持。作者声明没有利益冲突。
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