Treatment of Ovarian Disturbances In case of an ovulation, infrequent or irregular ovulation, ovaries are stimulated to ensure ovulation. It is essential in women with anovulatory cycles, but is also used in normally ovulating ovaries. Although the same regimen is used the nomenclature differs; Induction of Ovulation in An ovulation and Super ovulation in normal spontaneously ovulating women. In super ovulation the objective is to ensure ovulation, achieve ovulation at the desired time for the natural coitus or the ART procedure and Multiple follicle Development (MFD) to achieve better results in ART, IVF
Super ovulation is also useful in cases of unexplained infertility and male infertility coupled with intrauterine insemination (IUI). Because Ovulation is strictly monitored, it is called Controlled Ovarian Stimulation (COS). Controlled Ovarian Hyperstimulation (COH) is the medical treatment to induce the development of multiple ovarian follicles. Increased numbers of ova enhance the chances of fertilization by providing opportunity to the same number of sperms.
Ovarian stimulation is required in the women desirous of getting pregnant. Although seeking conception all these women are not infertile. There is tendency to delay childbearing & choose timing for conception for career, social or other reasons.
Choice of the ovulation treatment depends on gonadotrophins levels. In their normal levels, Clomiphene citrate can help otherwise is stimulated with gonadotrophins.
Clomiphene Citrate (CC) tablets are the most commonly used fertility treatment. CC is prescribed only in women with active ovaries. One tablet of 50 mg is starting dose, taken daily from Cycle Days 2 for 5 days. TVS is done on CD-12. If the largest follicle grows to > 17 mm ovulation is imminent. CC therapy is successful. If not TVS is repeated twice at 2 days intervals to see if a follicle grows to be > 17 mm,.
If no progress, proceed to next cycle with 2 & then 3 tablets of CC daily in the same way. If FD >17 mm achieved, CC therapy is successful; the same dosage schedule is repeated for 3 cycles.
It should be realized that CC is not a stimulatory drug. It blocks ovarian hormone’s negative feed back; pituitary thus freed releases available gonadotrophins which initiate FD. Indigenous gonadotrophins levels are not raised by increasing the CC dose over the effective dose.
Clomiphene Citrate & Human chorionic Gonadotrophins (hCG).It has become customary to use hCG in combination with CC. hCG administration is not necessary in all because in CC protocol, after suppression of negative feed back, the natural, spontaneous process of follicular growth sets in. hCG is administered where luteinization is not naturally taking place, i.e. LH levels are low and LH surge is not expected. hCG 5,000 or 10,000 units are administered in selective cases when FD is > 17 mm. It not only triggers LH surge but also provides luteal support. Ovulation is expected 36 hours later. The couple is advised to have sexual intercourse during this period.
It has become customary to use CC in all cases of infertility as a primary drug without selection which has lead to its misuse. Ovulation rate in selective population is >70 % but Pregnancy rates are lower due to
- Anti estrogenic effects on endometrium and on cervical mucus.
- Decrease in uterine blood flow
- Effect on tubal Transport.
- Detrimental effect on oocytes.
Marked release of LH in proportion to FSH sometimes occurs, temporarily changing LH: FSH ratio. Follicle maturation in such cases is impaired & ovulation delayed explaining lack of action in some women.
Controlled Ovarian Stimulation (COS) with extraneous Gonadotrophins. Direct ovarian stimulation is achieved with injections of synthetic gonadotrophins.
Gonadotrophins (Gn) Regimens: The selection of different hormone preparations is based on existing ovarian status of the woman determined by hormone assays. In woman with normal hormones pattern hMG can be used. For abnormal patterns usually FSH or rFSH are used. There are step up (starting with higher dose and reducing after seeing response), step down (starting with lower dose and increasing after seeing response) and sequential schedules (starting with a dose and changing it according to the response).
Monitoring by TVS and hormone assays (estrogen & LH levels) is necessary in order to assess the development of the follicles and to avoid the possibility of OHSS. If facilities lack observation of cervical mucus changes can help. If Estradiol is low on day-8 of the cycle, hCG is added to the FSH. FSH is continued until the day of hCG administration.
Adverse reactions seen are local reaction at injection site, fever, joint pains, flu like symptoms and Ovarian Hyperstimulation Syndrome (OHSS). In OHSS, hCG is delayed & dosage reduced