Understanding Reproductive Hormones

The rising progesterone level sends feedback to the pituitary gland, and further release of luteinizing hormone is suppressed.  The body now awaits a signal that fertilization has occurred.  If no fertilization has occurred, the corpus luteum degenerates, causing a decline in progesterone and estrogen to a lesser extent.   The declining estrogen levels (no estrogen produced by the follicular cells or the demised corpus luteum) permit the follicle-stimulating hormone levels to rise again.  The decline of progesterone causes the uterus wall lining to shed and precipitates menstruation.  We can now circle back to “Starting at the Beginning” above.

 

There are sometimes references to the follicular and luteal phases of the ovaries.   The first half of the menstrual cycle is called the follicular phase.   The luteal phase is dominated by the hormones secreted by the corpus luteum.

 

 

Follicle Stimulating Hormone (FSH)

 

Follicle-stimulating hormone is a hormone that stimulates follicles to grow.  These hormone levels fluctuate with a woman’s age.  Follicle-stimulating hormone is measured on days 2, 3, or 4 of a woman’s cycle.   A woman’s menstrual cycle is measured from the first day of her period (blood flow, not spotting), so Cycle Day 3 is the third day of her period.   A level under seven is considered normal if the woman is below the age of 34.  Follicle-stimulating hormone level below eight is ideal for women from 35 to 38 years old.  A level above ten is considered abnormal in all age groups.  Low levels are a problem in themselves.  Follicle-stimulating hormone levels are suppressed by luteinizing hormone and estrogen.  Therefore, low follicle-stimulating hormone levels could indicate that the ovaries are not making enough eggs, the luteinizing hormone and estrogen levels could be overactive, perhaps the pituitary gland is not working correctly, there may be a problem with the hypothalamus, or maybe the woman is very underweight.   If the ovaries have many follicles, then the multiple follicular cells will release a more significant amount of estrogen, and a large level of estrogen results in a slowdown in the amount of follicle-stimulating hormone released.  As the ovaries age, they release fewer hormones (mainly estrogen, but the ovaries release other hormones).   The result is that follicle-stimulating and luteinizing hormones can no longer perform their usual functions to regulate estrogen and progesterone.   In such a case, a woman’s body must work much harder to induce ovulation.  Fewer follicular cells can release estrogen when few follicles develop, so estrogen levels are lower.   Low estrogen will not give feedback to the pituitary gland to suppress the production of follicle-stimulating hormone.  Therefore, the release of the follicle-stimulating hormone is not suppressed, resulting in a higher follicle-stimulating hormone level.  A high level indicates that the donor may not be eligible to be an egg donor because the quality and quantity of her eggs are low.  Two quick qualifications: (1) an elevated follicle-stimulating hormone level does not mean a pregnancy is impossible, (2) ovaries react differently each month, so it is advisable to monitor follicle-stimulating hormone levels for a few months.

 

 

Estrogen (E2)

 

Estrogen is a female sex hormone that is produced mainly in the ovaries.  The adrenal glands also produce some estrogen, as do fat cells.  Estrogen is responsible for menstruation, menopause, reproduction, sex drive, and bone and blood health.  One of the hormones it works in concert with is progesterone, another female sex hormone.   Both female and male bodies have this hormone, but females create more. Estrogen is a hormone throughout a woman’s cycle, but the levels fluctuate.   The maturing follicle on the surface of the ovaries produces estrogen.  At a certain estrogen level, the pituitary gland releases a luteinizing hormone (which facilitates the release of the dominant egg).  In addition, the feedback from high estrogen levels causes the pituitary gland to reduce the follicle-stimulating hormone released.   

 

Estrogen levels are checked several times during an egg donor cycle: 1) Part of the day three baseline blood tests and 2) throughout the ovarian stimulation phase of the in vitro fertilization cycle.  Sometimes, an estradiol level is checked just before the cycle begins.

 

If the estradiol level is high on day 3, there is a problem.  On day 3 of the menstrual cycle, the follicles have not yet matured, so the body should have low estradiol levels. Remember that estradiol suppresses the release of follicle-stimulating hormones and that once the dominant follicle has reached a good size, the cells in the follicle’s fluid start releasing larger amounts of estradiol.   As the estradiol levels increase, the pituitary gland slows down follicle-stimulating hormone production. When estradiol level is at its peak, the pituitary gland is prompted to release luteinizing hormone, which triggers the release of the egg.  Therefore, if on Day 3, the follicle-stimulating hormone level is low, but estradiol is high, it could be an indication that the estradiol is artificially keeping the follicle-stimulating hormone level low when, in fact, the follicle-stimulating hormone level is high (which is a bad thing as a high level indicates poor ovarian reserve). 

 

Luteinizing Hormone (LH)

 

The Luteinizing hormone blood test measures the amount of luteinizing hormone secreted by the pituitary gland once estrogen levels reach a specific high number.  In women, luteinizing hormone levels rise mid-cycle and trigger ovulation within 24 to 36 hours.  This hormone also triggers the development of the corpus luteum, which in turn produces progesterone.  Higher-than-normal levels of luteinizing hormone indicate several disorders, including ovarian failure and polycystic ovary disease.

 

These three hormones (follicle-stimulating hormone, luteinizing hormone, and estradiol) can all be checked with a simple blood test performed on Cycle Day 3.  The average value ranges for the follicle-stimulating hormone, luteinizing hormone, and estradiol tests may vary among different laboratories, so it is important to get an accurate interpretation of the results from your fertility specialist.

 

 

Progesterone

 

The corpus luteum produces progesterone.  The corpus luteum is what remains of the ovarian follicle after releasing the egg.  Progesterone signals the uterus to prepare for possible implantation.  It also signals the pituitary gland to reduce luteinizing hormone production.  Interestingly, progesterone also causes a slight increase in body temperature.  This change in body temperature can be used to chart a woman’s cycle, i.e., that ovulation has occurred.

 

 

Human chorionic gonadotropin (HCG) is produced if fertilization and implantation occur.  Human chorionic gonadotropin prevents the corpus luteum from degenerating so that progesterone and estrogen levels remain high.  This is the hormone that is used in pregnancy tests.   It is also used as the trigger in an egg donor cycle that causes the eggs to mature and helps the ovaries release the eggs approximately 36 hours after the shot (similar to what the luteinizing hormone does in a natural cycle).   The timing of the trigger shot is important as the infertility doctor will aspirate the eggs just before the follicles rupture and release the eggs.

 

Antral Follicle Count (AFC)

 

An antral (resting) follicle is a small, fluid-filled sac containing an immature egg and can be seen, measured, and counted on Days 2, 3, and 5 using ultrasounds.  The number of antral follicles varies from month to month because ovaries behave differently from month to month.  Therefore, it is important to do this count before EVERY cycle.  Please do not be persuaded by an agency telling you that money can be saved using results from a prior egg donor cycle.  Skipping a redo on the follicle-stimulating hormone level testing is okay, but always do an antral follicle count before committing to an egg donor cycle.

 

A typical mid-30-year-old woman has an antral follicle count of 5-10 follicles per ovary or over 18.  Female age and antral follicle count are the best tools to estimate ovarian reserve, the expected response to ovarian stimulating drugs, and the chance for a successful pregnancy.   The number of antral follicles visible on ultrasound indicates the number of primordial follicles remaining in the ovary.  Each primordial follicle contains an immature egg that can potentially develop and ovulate.   When there are only a few antral follicles visible, there are far fewer eggs remaining as compared to when there are more antral follicles.   As women age, fewer eggs remain; therefore, fewer antral follicles will be seen on the ultrasound.   If the antral follicle count is over 35 (considered a high count), ovarian hyperstimulation syndrome is likely.  Sometimes, the ovaries respond poorly to stimulation meds, and very few mature follicles are seen.   Generally, the entire cycle is canceled if fewer than three mature follicles are seen on an ultrasound.  The problem with an antral follicle count is that it is observer-dependent.  One clinician may see eight antral follicles, while another will only see four.       

 

 

Anti-Müllerian Hormone (AMH)

 

The Anti-Müllerian hormone is a newer method available to predict ovarian reserve.   This hormone is a protein produced by cells in your ovarian follicles, so a high amount of Anti-Müllerian hormone indicates you have plenty of follicles.   Therefore, testing a woman’s Anti-Müllerian hormone levels in her blood is another tool to estimate how many eggs a woman has remaining (her ovarian reserve).  Unlike other hormones, Anti-Müllerian hormone levels do not fluctuate during the menstrual cycle, so the blood sample can be taken anytime.  Women are born with all the follicles they will ever have.  Therefore, a woman’s Anti-Müllerian hormone level will not increase with age.  This hormone is a good indicator of the quantity of eggs but does not measure the quality of the eggs.  Therefore, a high Anti-Müllerian hormone indicates there are lots of follicles and could be an indication of polycystic ovaries (PCOS) or the presence of cysts that do not contain any eggs.  It is perfectly possible that there are plenty of follicles containing eggs in addition to the cysts.  But there is also a high ovarian hyperstimulation syndrome (OHSS) risk.