Follicle Stimulating Hormone (FSH) is a gonadrotropin, glycoprotein polypeptide hormone containing drugs that are used to stimulate a follicle (egg) to develop and mature. It is one of the most important hormones involves in the natural menstral cycle as well as in pharmacological (drug-induced) stimulation of the ovaries especially for the development of multiple eggs for in vitro fertilization (IVF).
The reference range for FSH is as follows:
Age 8 years to adult:
Follicular phase: 3.1-7.96.7mIU/mL
In Males, age 0-7years <6.7mIU/mL while from age 8 years to adultis 1.3-19.3 mIU/mL
Development of FSH Drugs
The first FSH products were derived and purified from the urine of postmenopausal women. Because they were human derived, they contained impurities, notably luteinizing hormone (LH) was administered by intramuscular injection, which is painful and inconvenient.
More recent products include Gonal-F, and Follistim, which are produced using genetic recombinant technology. These FSH products are pure and can be given subcutaneously (just beneath the skin). Bravelle and Menopur are highly purified “human derived” products that can also be given subcutaneously.
Understanding the work of FSH
FSH is produced by the pituitary gland under the influence of Gonadotropin-releasing hormone (GnRH), also known as Luteinizing-hormone releasing hormone (LHRH), which is released by the hypothalamus. In a normal cycle, the levels of FSH vary in relationship to hormones such as estrogen.
When FSH is given by injection, it directly stimulates the recruitment and development of follicles in contrast to Clomid, which works at the hypothalamus. Numerous eggs are needed in IVF cycles as some are immature and cannot be fertilized. As patients undergo ovulation induction with FSH, they are carefully monitored by estradiol measurements, ultrasound to visualize the ovaries and follicles, and physical examination.
There is debate among physicians and embryologists as to the need for LH in FSH stimulated cycles. All physicians administer these products using individualized protocols for each patient. Many physicians believe that a minute quantity of LH causes a “better stimulation” in some patient groups. Mixed protocols using Follistim (FSH) and Bravelle, Menopur or Repronex are often used.
Possible FSH Side Effects
FSH should only be administered by a fertility specialist / Reproductive Endocrinologist thoroughly trained in its use. Patients must be monitored and dosages adjusted to avoid potentially serious side effects such as ovarian hyperstimulation. Most high order multiple births (triplets, or more) reported by the media are due to FSH stimulated intrauterine insemination (IUI) cycles that were not managed by a fertility specialist.
What produces FSH hormone?
Both FSH and LH hormone are produced by the pituitary gland at the base of the brain. When a woman goes into menopause she is running out of eggs in her ovaries. The brain senses that there is a low estrogen environment – and signals the pituitary to make more FSH hormone. More FSH is released from the pituitary in an attempt to stimulate the ovaries to produce a good follicle and estrogen hormone.
However, in a menopausal woman, the gas pedal is on the floor for the rest of her life – even though there are no follicles (or eggs) left. The woman’s body never gives up trying – FSH levels are permanently elevated. Women in menopause have high FSH hormone levels – above 40 mIU/ml. As women approach menopause their baseline FSH levels (day 3 of their cycle) will tend to gradually increase over the years. When they run out of follicles capable of responding, their FSH will be high and they stop having periods. If this happens in a woman under age 40, it is an indication for premature ovarian failure or primary ovarian insufficiency
Why measuring the FSH level on day 3?
Measuring a woman’s baseline FSH on day 3 of the cycle has been the usual trend ; (Some do it on day 2, 3, or 4) to have a clue as to whether she has normal “ovarian reserve”.
Therefore, if the baseline FSH is elevated the ovarian reserve is reduced and the egg quality as well. Some practical problems with the day 3 FSH test:
The cut off values used to say that egg quantity is good, OK, or poor is laboratory dependent. For example, and FSH of 11 in one laboratory may reflect good ovarian reserve – whereas a level of 11 in another lab using a different assay may indicate diminished ovarian reserve. While an abnormal result (high baseline FSH) tends to be very predictive of low egg quantity, a normal result does not necessarily mean that the egg quantity is good. There are a significant number of women with normal FSH values that have a reduced egg supply. The lower egg supply is not being reflected in their FSH value. This is why doingantral follicle counts and AMH levels can be useful. By doing multiple ovarian reserve tests, we are more likely to find an ovarian reserve problem if there is one.
This could be particularly true for women in their 40s. An infertile 44 year old woman with a normal FSH (for example ) still has a very low probability of conceiving and delivering a baby with in vitro fertilization – or with any other fertility treatment. The fact that she is 44 greatly diminishes her chances – even if her FSH is normal.
Young women (under 35) with elevated FSH levels tend to stimulate better and have a much higher IVF success potential than “older” women. The better egg quality in the younger women can compensate for the quantity problem if there is any.
Not with standing getting a donor egg of a younger female could be an alternative in case of several trials of IVF by older women.
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