The Impact of Serum Progesterone Levels on the Results ofIn VitroFertilization Treatments: A Literature Review

Abstract

The aim of this review is to analyze the relationship between preovulatory progesterone (P) rise and in vitro fertilization (IVF) pregnancy outcomes. It also investigates the sources and effects of rises in progesterone levels, including the underlying mechanisms and potential strategies in preventing its elevation during ovarian stimulation. Progesterone is produced in the early follicular phase in the adrenal gland, which shifts toward the ovaries prior to ovulation. Several factors contribute to the etiology of P level increase including the number of multiple follicles, the overdose of gonadotropins and poor ovarian response. Nowadays, the influence of the preovulatory P rise on IVF outcome remains controversial. Several authors have failed to demonstrate any negative impact, while others reported a detrimental effect associated with the rise of P. It seems that P rise (1.5 ng/ml or 4.77 nmol/l) may have deleterious effects on endometrial receptivity, namely, accelerating the endometrial maturation process that subsequently narrows the period for implantation and thus decreases pregnancy rates. Recent studies have proposed different cutoffs according to the ovarian response, which may be a little high in patients with high response in relation to those of normal response or low response. To prevent a P rise, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation, cryopreservation of all embryos and transfer in the natural cycle.

Lipid droplets in the ovine uterus during the estrous cycle: Effects of nutrition, arginine, and FSH

“…In this and other studies, serum P4 concentration was greater in FSH-treated than nontreated ewes at early and mid-luteal phases in sheep [91]. Similar effects of ovarian hyperstimulation or superovulation on peripheral P4 concentration have been reported for other species including humans and cows [40,44,[77][78][79]92]. Such differences between hyperstimulated vs. non-stimulated females are due to greater number of CL after gonadotropin treatment.…”

“…The effects of gonadotropin treatments on uterine functions affecting endometrial receptivity have been clearly demonstrated for humans and other mammalian species [38]. For example, in humans, gonadotropin treatment resulted in alterations of mRNA expression of receptors for steroids, and other hormones and growth factors in the endometrium, and in steroid serum concentrations [40,41,[77][78][79]. In cows, treatments with gonadotropins resulted in altered oocyte LD accumulation and blastocyst development, expression of genes that regulate metabolic activity of the embryo, serum profile of P4 and PG metabolites, milk E2 concentration, endometrial and embryonic gene expression, and uterine blood flow, secretory functions, morphology and vascular density [43][44][45][80][81][82][83][84].…”

The effects of low‐dose human chorionic gonadotropin combined with human menopausal gonadotropin protocol on women with hypogonadotropic hypogonadism undergoing ovarian stimulation for in vitro fertilization

“…Such lines of evidence demonstrate that low‐dose hCG will not cause early onset of luteinization of granulosa cells, which is recognized as an injury to the quality of oocytes. In other words, low‐dose hCG has proved to be safe and does not impact upon implantation, although previously the premature luteinization of granulosa cells was thought to be the most possible limitation of hCG compared with r‐LH . In addition, it is observed that P4 rises visibly the day after trigger with a much higher value in the control group.…”

Effect of low‐dose dexamethasone on patients with elevated early follicular phase progesterone level and pregnancy outcomes in IVF‐ET treatment: A randomized controlled clinical trial

“…Some investigators have demonstrated that elevated serum progesterone level during the follicular phase provides a suboptimal endocrine milieu for follicular growth and advances or disrupts endometrial receptivity. As a result, the pregnancy rate and live‐birth rate in fresh embryo transfer (ET) cycles are reduced …”

“…As a result, the pregnancy rate and live-birth rate in fresh embryo transfer (ET) cycles are reduced. [1][2][3] Even though the origin of serum progesterone throughout the follicular phase remains unclear, its production is a combination of secretion from the adrenals and the ovaries. [4][5][6] The adrenals are possibly the main source of serum progesterone during the early follicular phase, whereas the ovaries mainly contribute during the late follicular phase.…”