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Management of Infertility in Females

Dr. Umesh N. Jindal

Page 4

Topics

Recently more pure recombinant preparations prepared through genetic engineering have come in the market. Field trials have confirmed their efficacy.

The main indications of gonadotrophin therapy include CC failures, hypogonadotrophic-hypogonadism and controlled ovarian hyperstimulation (COH) for ART. Treatment with Gonadotrophins is very costly, time consuming and have potential serious side effects. Thus, the case must of selected very carefully after proper evaluation, counseling and complete infertility work up. Treatment should be monitored with serial USG and E2 (estradiol) measurements. Dose and duration of therapy depend on the indication, ovarian sensitivity, and target number of follicles to be recruited. In a patient with anovulation unifollicular ovulation is the aim, but 3-4 follicles are desirable in COH combined with IUI. For IVF, GIFT (gamete intrafallopian transfer) and ICSI (intra cytoplasmic sperm injection) 8-10 follicles give most satisfactory results.

Multiple gestation and hyperstimulation syndrome are the two major complications. These can be reduced to minimum with their judicious use. The most significant aspect of gonadotrophin therapy is that it achieves pregnancy in an otherwise untreatable situation. A 90% anovulation and 50 – 70% pregnancy rate can be expected.

Human Chorionic Gonadotrophin – Human Chorionic Gonadotrophin (hCG) a peptide hormone is naturally secreted exclusively by trophoblast since very early pregnancy. It has a structural and functional similarity with LH. Thus it makes an excellent surrogate for LH to trigger ovulation in CC or HMG induced cycles. When the follicle size is greater than 18 mm along with simultaneous thickening of endometrium to more than 8 mm, hCG 5000-10,000 IU I/M can be given. Ovulation occurs to 36-48 hours after the hCG. Intercourse or IUI or ovum-pick up can be timed accordingly. HCG also supports the corpus luteum when given in doses 1500-2000 IU I/M on day 3, 6, 9 post ovulation.

GnRH analogues – GnRH is an ultra short acting decapeptide secreted by hypothalamus. Long acting analogues have been synthesized. When given for short duration (1-2 days) these have a flare effect on secretion of gonadotrophins from anterior pituitary. If the administration is continuous, complete down regulation of gonadotrophin receptors of anterior pituitary occurs followed by complete suppression of FSH and LH secretion. Addition of these analogues to stimulation protocols in ART cycles have resulted in convenient schedules, low cancellation rates, better quality of oocytes and higher success rates.

Medical Management of Endometriosis – Endometriosis is an enigmatic disease characterized by ectopic endometrial glands and stroma. While infertility is easily understood in moderate and severe endometriosis which may cause structural distortion of tubes, ovaries and pelvic peritoneum. Minimal and mild disease is more frequently detected in infertile females than fertile counterparts, the mechanism of infertility remains elusive. There is no role of medical therapy alone in stage III and IV disease when fertility is the concern. In early disease, a 6 month trial of therapy may be given in young women with short duration of infertility. Success rates in general remain low. All medical methods rely on medical induction of temporary pseudo menopause and hypoestrogenic state. Continuous high dose gestogens, danazole – a testosterone derivative and GnRH-a are the three main options available. All these are costly, poorly tolerated and most importantly, add approximately a year of iatrogenic infertility to the duration of infertility. However, fairly satisfactory palliation of symptoms can be achieved when fertility is not desired.

Medical Management: Treatment of Infections – Pelvic infections, such as chlamydia, gonorrhoea, post-abortal and postpartum infections, pelvic inflammatory disease associated with intrauterine contraceptive devices, lead to permanent structural and functional damage to the fallopian tubes. Resurgence and alarmingly high incidence of TB make it an important cause of intractable infertility. The extent of damage depends on the severity and chronicity. Thus all pelvic infections must be prevented and treated early wherever possible. Medical treatment can only do the microbial clearance. Any structural or functional damage is more likely to be permanent.


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