Abstract：
OBJECTIVE: What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy\'s course?
CONCLUSIONS: 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.
BACKGROUND: 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.
METHODS: 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.
METHODS: Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center.
RESULTS: 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.
CONCLUSIONS: The retrospective study design and the small sample size can limit the accuracy of the estimates.
CONCLUSIONS: 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.
BACKGROUND: This study did not receive funding. The authors declare that there is no conflict of interest.
BACKGROUND: N/A.
CONCLUSIONS: 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.
BACKGROUND: 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.
METHODS: 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.
METHODS: Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center.
RESULTS: 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.
CONCLUSIONS: The retrospective study design and the small sample size can limit the accuracy of the estimates.
CONCLUSIONS: 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.
BACKGROUND: This study did not receive funding. The authors declare that there is no conflict of interest.
BACKGROUND: N/A.
摘要：
目的：黄体期卵巢刺激期间未发现自然受孕的风险是多少？
结论：未被发现的风险，自然受孕妊娠黄体期卵巢刺激低，似乎卵巢刺激不太可能损害妊娠。
背景：随机开始卵巢刺激似乎与早期卵泡刺激开始同样有效；并且它允许卵巢刺激独立于周期日和整个周期开始，按照患者\'和诊所\'的时间表，只要不打算在同一周期内进行新鲜胚胎移植。在黄体期开始卵巢刺激具有在刺激开始的时间点未被发现的可能性，已经发生的自然受孕。关于该事件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。
方法：这项回顾性观察研究，在2017年6月至2024年1月期间进行，分析了黄体期刺激，其中在IVF/ICSI的卵巢刺激治疗期间检测到自然受孕。黄体期刺激定义为排卵后和下一次预期月经出血之前开始卵巢刺激，在刺激开始当天或前1天，血清孕酮（P4）水平>1.5ng/ml。
方法：在三级转诊ART中心接受黄体期卵巢刺激的女性。
结果：共488个黄体期刺激周期纳入分析。黄体期刺激仅在开始卵巢刺激的前一天或前一天的阴性血清hCG测量后开始。10名患者（2.1％）在黄体期刺激开始时没有发现自然受孕。这些患者中有8例接受了GnRH拮抗剂方案的卵巢刺激，2例接受了孕激素刺激方案（PPOS）的卵巢刺激。重组FSH被用作所有患者的刺激药物，采用PPOS方案的患者接受了额外的重组LH治疗.取卵后检测到1次妊娠（0.2%），检测到另外9例妊娠,要么是由于血清孕酮水平持续偏高,要么是由于在取卵前孕酮水平初步下降后升高.在自然怀孕未被发现的周期中，中位刺激天数为8天(范围:6~11天),检测到妊娠时的中位血清hCG为59IUhCG(范围:14.91~183.1).从10名怀孕的患者中，三个病人接生了一个健康的婴儿,两名患者在总结数据时正在怀孕，三名患者有生化妊娠（患者年龄：30、39和42岁），一名患者异位妊娠需要输卵管切除术，和一名患者（年龄：34岁）有早期妊娠丢失。
结论：回顾性研究设计和小样本量会限制估计的准确性。
结论：总体而言，当进行黄体期刺激时，未检测到自然受孕的风险很小。在我们的队列中，似乎没有通过对胚胎的直接影响或通过对黄体功能的有害影响而间接地对妊娠产生不利影响。
背景：本研究未获得资助。作者声明不存在利益冲突。
背景：不适用。
结论：未被发现的风险，自然受孕妊娠黄体期卵巢刺激低，似乎卵巢刺激不太可能损害妊娠。
背景：随机开始卵巢刺激似乎与早期卵泡刺激开始同样有效；并且它允许卵巢刺激独立于周期日和整个周期开始，按照患者\'和诊所\'的时间表，只要不打算在同一周期内进行新鲜胚胎移植。在黄体期开始卵巢刺激具有在刺激开始的时间点未被发现的可能性，已经发生的自然受孕。关于该事件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。
方法：这项回顾性观察研究，在2017年6月至2024年1月期间进行，分析了黄体期刺激，其中在IVF/ICSI的卵巢刺激治疗期间检测到自然受孕。黄体期刺激定义为排卵后和下一次预期月经出血之前开始卵巢刺激，在刺激开始当天或前1天，血清孕酮（P4）水平>1.5ng/ml。
方法：在三级转诊ART中心接受黄体期卵巢刺激的女性。
结果：共488个黄体期刺激周期纳入分析。黄体期刺激仅在开始卵巢刺激的前一天或前一天的阴性血清hCG测量后开始。10名患者（2.1％）在黄体期刺激开始时没有发现自然受孕。这些患者中有8例接受了GnRH拮抗剂方案的卵巢刺激，2例接受了孕激素刺激方案（PPOS）的卵巢刺激。重组FSH被用作所有患者的刺激药物，采用PPOS方案的患者接受了额外的重组LH治疗.取卵后检测到1次妊娠（0.2%），检测到另外9例妊娠,要么是由于血清孕酮水平持续偏高,要么是由于在取卵前孕酮水平初步下降后升高.在自然怀孕未被发现的周期中，中位刺激天数为8天(范围:6~11天),检测到妊娠时的中位血清hCG为59IUhCG(范围:14.91~183.1).从10名怀孕的患者中，三个病人接生了一个健康的婴儿,两名患者在总结数据时正在怀孕，三名患者有生化妊娠（患者年龄：30、39和42岁），一名患者异位妊娠需要输卵管切除术，和一名患者（年龄：34岁）有早期妊娠丢失。
结论：回顾性研究设计和小样本量会限制估计的准确性。
结论：总体而言，当进行黄体期刺激时，未检测到自然受孕的风险很小。在我们的队列中，似乎没有通过对胚胎的直接影响或通过对黄体功能的有害影响而间接地对妊娠产生不利影响。
背景：本研究未获得资助。作者声明不存在利益冲突。
背景：不适用。
