A normal menstrual cycle requires a precisely timed series of events that interrelate to allow for regular ovulation.
These events are important to understand since they allow physicians to manage fertility care.
(Available Drawing: Hypothalamus-Pituitary-Ovarian Axis)
Available Case Reports:
Only the recruited follicles will respond to the signal to mature, which is a hormone named follicle stimulating hormone (FSH).
Research suggests that this small group of recruitable follicles present at the onset of a cycle has actually been prepared
specifically for the cycle over a 3-6 month period of time.
No recruited follicle will enter more than one cycle of maturation, such that if a follicle begins to mature with
FSH stimulation the follicle will either ovulate or will degenerate during that month.
Fertility medications called human menopausal gonadotropins (menotropins) have FSH as their active ingredient to
stimulate egg maturation. In the presence of excess amounts of FSH all recruitable follicles may develop simultaneously.
At the time of (egg) maturation during cycles using fertility medication, there may be more than 10-25 mature eggs
in the ovaries (as compared to only one mature egg in the typical natural cycle).
The goal of menotropin therapy generally is to mature as many eggs as possible. Since only that month’s recruited follicles
can respond to FSH and develop you are not using eggs that would ever enter another cycle. Therefore, you will not have
early menopause due to menotropin therapy.
(Available Drawing: Developmental Timecourse)
Circulating FSH concentration changes throughout the cycle such that only one mature egg is usually produced at ovulation.
FSH concentration increases prior to the onset of menstrual flow to rescue some of the eggs within the recruitable pool
of follicles from degeneration. These eggs begin to mature.
Within the first 5-7 days of the cycle one of the developing follicles out competes the others for available FSH.
This becomes the "dominant follicle" that goes on to ovulate.
|Photograph of a transvaginal ultrasound revealing a "typical" right ovary on cycle
day 3, with several small antral
follicles that range from 4-10 mm in diameter.
It is uncommon for 2 eggs to mature simultaneously in a cycle, with the twinning rate for natural cycles in the USA
about 1 in 80 to 1 in 90 pregnancies.
Circulating FSH concentration decreases as ovulation approaches to enhance atresia (degeneration) of the maturing
Fertility medications used to increase the number of fully matured eggs during a given cycle should be initiated
prior to the selection of the dominant follicle. This will enhance the yield of fully mature eggs.
(Available Drawing: Hormone Changes During Menstrual Cycle)
A sudden rapid increase in both the follicular diameter (size) and the circulating estrogen concentration
(function) occurs just prior to complete egg maturation. The increase in diameter is identifiable by ultrasound.
The increase in estrogen level is identifiable with close monitoring of blood estradiol concentrations.
Monitoring findings from ultrasounds and in the woman’s bloodwork allows the infertility specialist to interpret
changes in egg development and adjust therapy.
Available Case Reports:
This sudden increase in LH concentration, the "LH surge," is the trigger for both "the egg" to undergo its final
maturational step and for "the ovary" to undergo the final changes required to release the mature egg into the pelvis.
Injections of hCG (Profasi) when the egg(s) is mature can mimic the LH surge since the hCG and LH molecules are
structurally very similar. Actually hCG and LH use the same cellular receptors. This then triggers ovulation about
one and a half days later.
Detection of the LH surge (as LH excreted in urine) is the basis of the commercially available ovulation predictor
kits (purchased in the pharmacy).
Available Case Reports:
A major difference between the follicular cyst and the corpus luteum cyst is their hormone production.
The predominant sex steroid produced by the follicular cyst is estrogen and that of the corpus luteum cyst is progesterone.
Granulosa cells are cells that line the inside of both of these cysts and are capable of producing either estrogen
or progesterone. Cholesterol is the starting material for either of these hormones and its molecular structure is
changed using proteins called enzymes. The activity of the enzymes that change cholesterol into either estrogen or
progesterone can be enhanced or suppressed within these granulosa cells.
Under conditions present prior to ovulation the granulosa cells produce mostly estrogen and under the conditions present
following ovulation these cells produce mostly progesterone.
Prior to ovulation, high circulating estrogen concentrations act on the endometrium (uterine lining) to stimulate growth
that results in an increased endometrial thickness. Following ovulation, the high circulating concentration of progesterone
acts on the endometrium to stabilize it and prepare it for the implantation of an embryo.
Inadequate progesterone effect during the luteal phase of the menstrual cycle (a "luteal phase defect") can be treated
with supplemental progesterone (oral micronized progesterone, vaginal suppositories, vaginal gel applicator, or by
intramuscular injection of progesterone in oil). Alternatively, supplemental hCG can be given as injections every few
days following ovulation (to enhance the ovary’s own progesterone production) or clomiphene citrate can be taken by mouth
in the follicular (preovulatory) phase to increase the final size of the follicle prior to ovulation (so that there are
more granulosa cells to then produce progesterone in the luteal phase).
Supplemental progesterone for a luteal phase deficiency is usually continued until about 10-12 weeks gestation (8-10 weeks
from fertilization). The placenta takes over progesterone production from the ovarian corpus luteum during this time, so
that further supplementation is not necessary.
During this period of uterine receptivity the endometrial lining is ideally prepared to allow for embryo implantation.
In most cases embryos will only implant and grow normally if present in the cavity during this window of receptivity.
Progesterone is believed to be the major determinant of the window of receptivity, however, many other candidate
hormones and protein messengers are also being considered as the research on molecular mechanisms of implantation
continues to grow
The duration of the window of uterine receptivity in humans is thought to be about 3 days
During cycles of In Vitro Fertilization (including frozen embryo transfer cycles and donor egg cycles involving egg recipients)
the success rate (in terms of implantation or pregnancy) relates to the hormonal preparation of the endometrium (uterine lining).
If progesterone production, or the uterine response to the progesterone produced, is not adequate then the lining of the
uterus may be inadequate for embryo implantation. This situation can lead to either infertility if the lining does not
become receptive or recurrent pregnancy loss if the lining is receptive for implantation but the embryo cannot develop normally.
LH stimulates the enzymes within the corpus luteum cyst to produce progesterone for only about 2 weeks following ovulation.
If the woman becomes pregnant the placental cells that grow into the uterine lining and establish contact with the maternal
circulation produce a hormone called human chorionic gonadotropin (hCG). The hCG molecule produced by placental cells
(syncytiotrophoblast cells) is structurally similar to LH (they share the same receptors on the ovary to produce similar
In a pregnancy cycle, the maternal circulation begins to have a detectable hCG concentration about 7 to 8 days after
fertilization (fertilization occurs within a day or so of ovulation). This hCG then takes over (by acting like LH) the
stimulation of progesterone production by the corpus luteum cyst.
If the woman does not become pregnant, then there is no hCG to take over the role of LH in the support of the corpus luteum cyst.
Thus, the corpus luteum cyst deteriorates, the progesterone concentration supporting the uterine lining declines and the
uterine lining that has grown in preparation for pregnancy is shed (as the menstrual flow).
Menstrual flow sometimes becomes a monthly reminder that is associated with the pain and frustration often felt by couples
with an infertility problem.