Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization?

This  is an important question. IVF cycles are  monitored with serial measurements of estrogen ,  LH ,and Progesterone. At times , towards the last day of stimulation  we observe a slight rise of progesterone. some have questioned whether this progesterone level increase ( slight increase  not majour ovulation increases of 2 or 3) reduces the chance of pregnancy.

The short answer to this question is "the best available evidence does not support an association between progesterone elevation on the day of hCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF".

This is based on a large meta analysis that you can find here

What is the Luteal Phase?

The luteal phase (or secretory phase) is the latter phase of the menstrual cycle(in humans and a few other animals). It begins with the formation of the corpus luteum and ends in either pregnancy or luteolysis. The main hormone associated with this stage is progesterone which is significantly higher during the luteal phase than other phases of the cycle. Some sources define the end of the luteal phase to be a distinct "ischemic phase".

Hormonal events

After ovulation, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into the corpus luteum. It continues to grow for some time after ovulation and produces significant amounts of hormones, particularly progesterone, and to a lesser extent, estrogen. Progesterone plays a vital role in making the endometrium receptive to implantation of the blastocyst nd supportive of the early pregnancy; it also has the side effect of raising the woman's basal body temperature.

Several days after ovulation, the increasing amount of estrogen produced by the corpus luteum may cause one or two days of fertile cervical mucus. lower basal body temperatures, or both. This is known as a "secondary estrogen surge".

The hormones produced by the corpus luteum also suppress production of the FSH and LH that the corpus luteum needs to maintain itself. With continued low levels of FSH and LH, the corpus luteum will atrophy.The death of the corpus luteum results in falling levels of progesterone and estrogen. These falling levels of ovarian hormones cause increased levels of FSH, which begins recruiting follicles for the next cycle. Continued drops in levels of estrogen and progesterone trigger the end of the luteal phase: menstruation and the beginning of the next cycle.

The average length of the human luteal phase is fourteen days. Between ten and sixteen days is considered normal, although luteal phases of less than twelve days may make it more difficult to achieve pregnancy. While luteal phase length varies significantly from woman to woman, for the same woman the length will be fairly consistent from cycle to cycle.

The loss of the corpus luteum can be prevented by implantation of an embryo: after implantation, human embryos produce human chorionic gonaotropin (hCG). hCG is structurally similar to LH and can preserve the corpus luteum .Because the hormone is unique to the embryo, most pregnancy tests look for for the presence of hCG. If implantation occurs, the corpus luteum will continue to produce progesterone (and maintain high basal body temperatures) for eight to twelve weeks, after which the placenta takes over this function.

Luteal phase defect

Luteal phase defect (LPD) occurs when the luteal phase is shorter than normal, progesterone levels during the luteal phase are below normal, or both. LPD is believed to interfere with the implantation of embryos.

Can Progestrone Supplementation Prevent Miscarriages?

Based on the Chocrane Database Review the answer is : probably not. But is does seem to prevent further losses in women with 3 or more miscarriages. This is why in the end we end it prescribing it quite liberally. The review states quite clearly that the type of progesterone (vaginal vs injectable) makes no difference in therms of outcome. So don't believe it if they tell you that the oil injection is any better. Abstract is below

Abstract

Background

Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilised egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, progestogens have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage.

Objectives

To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage.

Search strategy

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2008), CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), CINAHL (1982 to June 2006), NHMRC Clinical Trials Register (June 2006) and Meta-Register (June 2006). We searched references from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works.

Selection criteria

Randomised or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage.

Data collection and analysis

Two review authors assessed trial quality and extracted data.

Main results

Fifteen trials (2118 women) are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (Peto odds ratio (Peto OR) 0.98; 95% confidence interval (CI) 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.

In a subgroup analysis of three trials involving women who had recurrent miscarriages (three or more consecutive miscarriages), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.38; 95% CI 0.20 to 0.70). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment.

Authors' conclusions

There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.

Source: Cochrane Database