A number of patients have asked why the transfer was cancelled because of high P in the current egg collection cycle. Combining the recommendations of China Laboratory Medicine, relevant literature and our practice, let’s understand the function of progesterone and its clinical significance. Progesterone (P) is produced by the granulosa luteal cells and follicular membrane luteal cells of the follicle and the placenta. Cholesterol is the raw material for the synthesis of progesterone (see Figure 1). The granulosa cells can respond to LH stimulation and secrete estrogen and progesterone before ovulation, and after the LH peak induces ovulation, the follicles luteinize and the granulosa cells’ ability to synthesize P is further enhanced. The main function of P is to convert the proliferating endometrium into a secretory endometrium with interstitial metaplasia-like changes, preparing the fertilized egg for implantation and subsequent embryonic development. The activity of ovarian follicles and corpus luteum can be inferred from the rise and fall of P concentration, therefore serum progesterone determination is mainly used in clinical practice to detect ovulation and normal function of corpus luteum in pregnant women and evaluation of early pregnancy. Figure 1: P concentration during the menstrual cycle: follicular phase: 0.14~1.61ng/ml, generally <3.15ng/ml; rising significantly after ovulation, up to 15~32.2ng/ml in the mid-luteal phase; then decreasing, reaching the lowest level in the premenstrual phase. To determine ovulation: mid-luteal P>5ng/ml indicates ovulation; 2. To diagnose luteal insufficiency (LPD): mid-luteal P<10ng/ml, or the sum of P measured three times on days 5, 7 and 9 after ovulation <10ng/ml, or P<15ng/ml before 10 weeks of pregnancy; 3. To identify ectopic pregnancy: patients with ectopic pregnancy have low P levels; So here comes the point: why do those with high P Cancellation of the current cycle of transplantation? Possible reasons for high progesterone High number of mature follicles: Serum P levels during controlled ovulation promotion (COS) usually reflect the accumulation of the normal amount of P secreted by each developing near-mature follicle, so too many developing follicles may cause high P, which to some extent also reflects good follicle maturation and better COS results. High E2 level: reflects high P due to multiple follicular development. In addition, endometrial tolerance is synergistically regulated by E2 and P. High E2 may influence endometrial tolerance by affecting P levels and activity and interfering with endometrial gene expression. High dose of FSH: The purpose of high dose of FSH in COS is to promote multiple follicle development and therefore can cause high P. Also, high doses of FSH can cause an increased ability of granulosa cells to acquire steroids, resulting in increased conversion of cholesterol to P. Relative deficiency of LH: According to the two cell-two gonadotropin theory, P is converted to androgens by the action of LH in follicular membrane cells, and then androgens are converted to estrogens by the action of FSH-induced aromatase in follicular granulosa cells (see Figure 2). That is, LH reduces circulating P levels by increasing the conversion of P to androgens. Therefore, those who use FSH to promote ovulation are more likely to have high P than those who use HMG (1:1 FSH:LH activity) to promote ovulation. Figure 2: When a trend toward elevated P is found in COS, it may be possible to increase the Leroy (LH) shot or HMG to adjust COS dosing in hopes of suppressing the trend toward high P by compensating for the relative lack of LH. Consequences of high progesterone Studies have shown that premature elevation of P during COS slows down the proliferation of the endometrium and prematurely converts it to the secretory phase, which leads to thinning of the endometrium and affects endometrial tolerance rather than pregnancy outcome by affecting egg quality. Currently, our center often uses the criteria of three consecutive P>1.0ng/ml during superovulation or a single P>1.5ng/ml, and recommends to cancel the transfer and freeze the whole embryo in parallel with this cycle.