Almost every doctor and health care manager has at least for once prescribed an ovulation inducing drug especially clomid (serophene tamoxiphen (Nolvadex)).
Apart from its abuse, some patients go on to increasingly and persistently take clomid, not only at the wrong time but even above 400mg daily for more than 5 days.
Continuous hyperstimulation of the ovaries may however result in large sized ovaries, cysts and tumors, and eventually lead to early menopause with hot flushes, palpitation etc.
Many users of these agents do not even know the reaction pathway of modus operandi of clomiphene products. They are not aware that clomid is a selective estrogen receptor modulator that raises the gonadotropins production by slowing down negative feedback from estrogen on the hypothalamus.
It is necessary to be informed about the following:
The importance of not allowing non-trained or incompetent personnel to handle these agents
The dangers of depleting the woman’s ovarian reserve of oocysts and exhausting ovarian activity and accelerating the woman’s journey into menopause
The dangers of complications arising from abuse of ovulation inducing drugs
The concomitant psychological task if these administrations fail because of wrong application regarding timing and dosage.The risk of multiple pregnancies with its attendant economic embarrassment, especially for the poor (with triplets and quadruplets).
The doctor should therefore avail himself of modern techniques of identifying the follicles, its rupture and size (folliculometry) by ultrasound scanning, BBT etc. It is not enough for the woman to feel slippery amid cycle or pain. Ovarian hyperstimulation must be avoided.
Endocrine-histo-anatomical illustration
Normally, a woman should produce only one follicle or rarely two at each menstrual cycle. If she starts her menses at menarche around 14 or 15 years of age and acceptably reproductive by age 16 through age 40 (that is, a period of 25 years), then at 2 follicles per month for 12 months give a total of 24 eggs and for 25 years, she would have produced a grand total of 600 eggs before menopause sets in.It must be recognized that this number of eggs is programmed at birth and designed to end at the expiration as the capacity of the individual. Consequently, if hyperstimulation is administered on her to produce 3 or 4 eggs, her ovarian reserve would have been depleted to drive her to early menopause.
The menstrual cycle
The menstrual cycle has 3 main phases:The productive phase or phase of recruitment or proliferative phase, when the eggs start to form under the influence of follicle stimulating hormone FSH/E2
The selection or ovulatory phase, mostly controlled by luteinizing hormone and modulated by prolactin and other hormones notably T4, E, TSH. In this phase, only one follicle gets selected (survival of the fittest) and prepared by progesterone.
The secretary phase or the phase of endometrial preparation for implantation largely modulated by progesterone.
Ovulation induction techniques
Ovulation induction would therefore consider two basic situations:Minor amenorrhoea
Anovulation
Minor (secondary) Amenorrhoea which is the activity of the hypothalamus-pituitary-ovarian integrity has to be established. This is basically done by progesterone withdrawal technique. (Primolut-n , P/N orprovera, 5mg/10mg x 5 days).
Once this produces eumenorrhoea (menses), then ovulation has to be induced with ovulatory agents such as clomid from the 2nd or 3rd day. Although some doctors prefer 5th day cycle, early stimulation is more appropriate and advised.
If on the other hand, progesterone withdrawal fails to restart menses, then further examination has to be employed, mostly hormonal and sonographics or x-ray of sella turcica to remove pivititary tumor etc. Menopausal hormones, HMG, menotropins that contain FSH/LH 75 IU are good ovulation inducers.
The follicles are then formed and are monitored by folliculometry at maturity, human chorionic gonadotropins (HCG) could be required to complete ovarian stimulation such as rupture of the mature eggs (at scan diameter > 1.7m) to release oocytes for either natural processes or IVF. Gonadotropin releasing hormone can also be employed to trigger final oocyte maturation. These drugs are available as clomid-metformin TX IN pcos of (9 IU cophage).
The rationale of using metforin is that some women with polycystic ovarian syndrome have some measure of insulin assistance. However, all the basic diabetes profile tests must be carried out prior to this test.
What constitute abuse to these agents, especially clomid?
The following practices are considered to constitute abuse to these agents:Recklessness and high cost.
Trial and error in use; if clomid fails, try FSH (profasi), if it fails, try GnRH, etc.
Start administration immediately, no history, no ultrasound scan, no respect for the phases of menses, no respect for dosage.
An appropriate approach should be:
Ascertain the integrity of the hypothalamic-pituitary-ovarian system and activity by laboratory test and scans.
Carry out all necessary laboratory tests including HIV, Australian antigens, Hb, urinalysis, etc
Ascertain the potency of the tubes (HSG) and uterus (scan, Asherman syndromes), before embarking on ovulation induction.
Note that all these tests cost money but also save money.
Conclusion
Oocytogenesis does not last all women’s lifespan, unlike spermiogenesis in the man.Depleting ovarian reserve can result in early menopause, with amenorrhoea, hot flushes, insomnia, palpitation etc.
Ova stimulation can cause ovarian tumors and cyst formation and eventual laparotomies.
Ova stimulation can cause multiple pregnancies with its associated emotional and economical factors.