IVF Department, ART Fertility Clinic, Abu Dhabi, UAE.
Reproductive Unit, UZ Gent, Gent, Belgium.
Hum Reprod. 2024 Oct 1;39(10):2268-2273. doi: 10.1093/humrep/deae165.
What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course?
The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy.
Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy.
STUDY DESIGN, SIZE, DURATION: This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center.
A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss.
LIMITATIONS, REASONS FOR CAUTION: The retrospective study design and the small sample size can limit the accuracy of the estimates.
Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort.
STUDY FUNDING/COMPETING INTEREST(S): This study did not receive funding. The authors declare that there is no conflict of interest.
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黄体期卵巢刺激期间未检测到自然受孕妊娠的风险是多少，它如何影响妊娠过程？
黄体期卵巢刺激期间未检测到自然受孕妊娠的风险较低，而且卵巢刺激似乎不太可能损害妊娠。
随机启动卵巢刺激似乎与早期卵泡刺激启动同样有效；并且只要在同一周期内没有新鲜胚胎移植的意向，它允许根据患者和诊所的时间表独立于周期日开始并贯穿整个周期进行卵巢刺激。在黄体期开始卵巢刺激可能会导致在刺激开始时已经发生的未被检测到的自然受孕妊娠。关于这种情况的发生率以及卵巢刺激对现有妊娠过程的可能影响的数据很少。
研究设计、大小和持续时间：这项回顾性观察性研究于 2017 年 6 月至 2024 年 1 月进行，分析了黄体期刺激，在接受 IVF/ICSI 的卵巢刺激治疗期间检测到自然受孕妊娠。黄体期刺激定义为排卵后和下一次预期月经出血前开始的卵巢刺激，在刺激开始当天或前一天血清孕激素（P4）水平>1.5ng/ml。
参与者/材料、设置、方法：在三级转诊 ART 中心接受黄体期卵巢刺激的女性。
共有 488 个黄体期刺激周期被纳入分析。黄体期刺激仅在刺激开始当天或前一天进行血清 hCG 阴性测量后开始。10 名患者（2.1%）在黄体期刺激开始时出现未被检测到的自然受孕妊娠。这些患者中有 8 名接受 GnRH 拮抗剂方案的卵巢刺激，2 名接受孕激素预刺激方案（PPOS）。所有患者均使用重组 FSH 作为刺激药物，接受 PPOS 方案的患者接受额外的重组 LH。1 例（0.2%）妊娠在取卵后检测到，其他 9 例妊娠是由于血清孕激素持续升高或取卵前初始下降后孕激素水平升高而检测到的。在有未被检测到的自然受孕妊娠的周期中，中位数刺激天数为 8 天（范围：6-11 天），中位数血清 hCG 检测到妊娠时为 59IU hCG（范围：14.91-183.1）。在 10 名妊娠患者中，3 名患者分娩了健康婴儿，2 名患者在总结数据时仍有妊娠，3 名患者发生生化妊娠（患者年龄：30、39 和 42 岁），1 名患者发生异位妊娠需要输卵管切除术，1 名患者（年龄：34 岁）发生早期妊娠丢失。
局限性、谨慎的原因：回顾性研究设计和样本量小可能会限制估计的准确性。
总体而言，黄体期刺激时发生未检测到的自然受孕妊娠的风险较小。在我们的队列中，似乎没有通过直接作用于胚胎或间接通过对黄体功能的不利影响对妊娠产生不利影响。
研究资金/利益冲突：本研究未获得资金。作者声明没有利益冲突。
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