A number of patients have asked why the transplant was cancelled because of high P in the current egg collection cycle. Relevant literature and our center’s practice, let’s understand the function of progesterone and its clinical significance.
Progesterone (P)
Progesterone is produced by the granulosa lutea 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 proliferative 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: 0.14-1.61 ng/ml, generally <3.15 ng/ml
rises significantly after ovulation, reaching 15-32.2ng/ml in the mid-luteal phase
Then decreasing, reaching the lowest level in premenstrual period
1.Determination of ovulation: mid-luteal P>5ng/ml indicates ovulation.
2.Diagnosis of 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. Identification of ectopic pregnancy: P levels are low in patients with ectopic pregnancy, usually
So here comes the point: why is this cycle cancelled for those with high P?
I. Possible causes of high progesterone
1. Excessive 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 excessive follicular development may cause high P. To some extent, it also reflects good follicular maturity and better COS results.
2. High E2 level: reflects high P due to multiple follicular development. In addition, endometrial tolerance is synergistically regulated by E2 and P. High E2 can affect endometrial tolerance by influencing P levels and activity and interfering with endometrial gene expression.
3. High dose of FSH: The purpose of high dose of FSH in COS is to promote multiple follicle development, therefore it can cause high P. At the same time, high dose FSH can cause an increased ability of granulosa cells to obtain steroids, which increases the conversion of cholesterol to P.
4. Relative deficiency of LH: According to the two cell-two gonadotropin theory, P is converted into androgens by the action of LH in follicular membrane cells, and then androgens are converted into 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 of elevated P is detected in COS, it may be possible to increase Leroy (LH) shots or HMG to adjust COS dosing in the hope of suppressing the trend of high P by compensating for the relative lack of LH.
Second, the 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.