For Doctors

What is FSH?

FSH is Follicle Stimulating Hormone, and it is produced by the brain (via the pituitary gland) to stimulate follicles in the ovary to grow. When the brain realises that there is low E2 around (ie at the time of a period), and a further group of follicles should be recruited to start another cycle, the blood level of FSH rises, but generally to not more than 9iu/l. If more FSH than 9iu/l is produced at the time of a period, the brain has somehow realised that to stimulate follicles to grow, more FSH is required than is normal – and the usual reasons for this are that the number of follicles in the ovary is low, or there is some problem within the follicles that the FSH needs to overcome to stimulate another menstrual cycle.

What is E2?

E2 is the steroid hormone that is produced by the cells lining the ovarian follicles in response to FSH, and the very high levels of E2 within the leading follicle nourish and mature the egg.  Some E2 reaches the blood to cause the lining of the uterus to grow, the secretion of ovulatory cervical mucus, and to provide feedback to the brain and pituitary that another cohort of follicles has been recruited and is growing. The level of FSH then falls due to negative feedback by E2.

Why measure around Day 2?

At this time, E2 is at its lowest so FSH should be at its highest. If the E2 level on Day 2 is > 200pmol/l, then follicle growth will have already started, and the measurement of the FSH is not reliable because the raised E2. will have already started to suppress the FSH level.   This commonly happens in older women. From a functional point of view, early follicle growth may mean the endometrium does not have enough time to develop before ovulation occurs, leading to asynchronicity between the egg and the endometrium, and hence a reduced chance of implantation. 

Possible interpretation of results are:

1. FSH < 9 iu/L; E2 < 200pmol/l = Normal basal follicle function, and normal amount of FSH being produced to stimulate the ovarian follicles
2. FSH >9 iu/l; E2 < 200 pmol/l= Brain responds to low ovarian reserve by producing more FSH to try to recruit a follicle. Ie. the brain is upping the production of its own fertility drug in recognition that there is something not right with follicle development.
3. FSH < 9 iu/l; E2 > 250 pmol/l= Ovary is racing ahead in follicle development, and correct interpretation of the FSH result is not possible because the E2 level is not basal.

1. FSH > 9 iu/l; E2> 250 pmol/l= Ovary is racing ahead of follicle development, and although interpretation of the FSH result is compromised by raised estra., it is likely that were the estra. to be basal (ie< 200pmol/l), the FSH would be even higher.

Day 21 Progesterone Measurement 

The corpus luteum is the gland formed in the ovary from the ovulated follicle(s). It makes progesterone and  and E2 that is secreted in to the blood and causes the lining of the uterus to become secretory. Blood level of progesterone in the middle of the luteal phase > 30nmol/l suggest that the endometrial effect of the progesterone is likely to be sufficient to assist an embryo implanting in the uterus. This progesterone in the blood also feeds back to the pituitary to ensure that little FSH is produced. There is no value in measuring the hormones FSH, LH and E2 at the same time as a Day 21 progesterone because their interpretation is not of any value if the progesterone is raised, as it should be in the mid-luteal phase. 

Why Day 21?

This day is chosen on the assumption that the women are having a 26-30 day cycle, and luteal phase is normal and lasts about 10-14 days after ovulation.  Thus, assuming ovulation is between Days 12-16 , Day 21 is the middle of the luteal phase when the production of progesterone from the corpus luteum gland peaks in an ovulatory cycle (and if there was then pregnancy, the HCG would prevent the corpus luteum from then dying and it would produce even more progesterone).  If ovulation has occurred later than Days 12 – 16, then the progesterone check would be better done a few days later so as to strike the middle of the luteal phase. Conversely, if ovulation has occurred earlier than Day 12, an earlier progesterone test at about Day 18 is required.

Progesterone levels should be interpreted with respect to the number of days before the onset of the next period. Luteal function ( and hence ovulation) cannot be assumed if the period starts < 5 days later or > 9 days after the blood test.

Possible interpretation of results assuming the test is properly timed are:

1. Progesterone  > 30nmol/l– ovulation has occurred and the corpus luteum is producing sufficient progesterone to induce adequate secretory changes in the endometrium to assist implantation.
2. Progesterone 3-30 nmol/l– ovulation has occurred > 10 days ago or < 5 days ago, or if ovulation did occurr 5-10 days ago, the level is probably not adequate to sustain endometrial growth for satisfactory implantation. 
3. Progesterone >120 nmol/l– two or more follicles have been recruited
4. Progesterone < 3nmol/l– no ovulation in previous 14 days.