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Ovulation Induction refers to therapeutic restoration of the release of one egg per cycle in a women who is not ovulating at all or ovulating irregularly. It differs from Ovarian Stimulation where we aim to have multi follicular development specially in unexplained infertility. Ovulatory disturbances are present in about 15 – 25% of infertile couples and majority of these women have polycystic ovaries.
Insulin Sensitizers like Metformin or Myoinositol
Clomiphene Citrate
Aromatase Inhibitors
Gonadotropins
Insulin Sensitizers: Weight reduction either by life style modification or by insulin sensitizer like metformin or myoinositol constitutes the first and foremost modality in obese patients to restore ovulation followed by other therapeutic drugs like Clomiphene Citrate.
Clomiphene Citrate: . It’s the first line and most ubiquitously used drug for ovulation in PCOS patients. It’s a weak synthetic estrogen, with antiestrogenic properties. It is usually given in a starting dose of 50- 100 mg, from day 2/3/5 of the cycle for 5 days. Ovulation is expected to occur 7-10 days after the last tablet in 80- 85% of treated women and 40% conceive . Side effects are usually mild and usually occur in the form of hot flushes, abdominal distention, bloating, nausea, vomiting, headache. This drug is safe, cheap, easy to administer and highly effective for ovulation induction.
Aromatase inhibitors (Letrozole , Anastrazole): 20-25 % of women are resistant to clomphene citrate and do not ovulate . Aromatase inhibitors(AI) originally developed and approved for treatment of breast cancer are currently being used as an alternatives to clomiphene with increased frequency. Letrozole is a third generation aromatase inhibitor (AI). The AI, letrozole, is effective in ovulation induction in women with PCOS resistant to clomiphene citrate and ovarian stimulation for intrauterine insemination and in vitro fertilization (IVF). Letrozole is an attractive option with its oral route of administration, cost, safety profile and effectiveness in ovulation induction and ovarian stimulation. Letrozole gives comparable ovulation, pregnancy and miscarriage rates to clomiphene .
Gonadotrophins: May be used to stimulate follicular development and induce ovulation. They may be used for PCOS women who have failed to respond to oral drugs like Clomiphene Citrate or Letrozole. They are also used for Controlled Ovarian Stimulation, specially when combined with IUI in unexplained infertility. Gonadotrophin treatment requires daily injection with either HMG, Urinary FSH or Recombinant FSH. Gonadotropins require intensive follicle monitoring by Ultrasound and to be supplemented with serum Serum Estradiol levels when required. The pregnancy rates are better than clomiphene citrate but the cost increases and there are increased chances of multiple pregnancy and OHSS.
IUI is depositing of washed and concentrated motile sperm into uterine cavity through cervix using a fine plastic catheter. Intrauterine insemination (IUI) is widely accepted as the first line treatment for treating infertile couples.
IUI is a first line treatment for following cases:
Low sperm count
Decreased sperm motility
A hostile cervical mucus
Erectile or ejaculatory dysfunction
Sexual dysfunction
Unexplained infertility
Azoospermic males when IUI is done with donor
IUI with cryopreserved Semen when the husband is working abroad
It may be done in a natural cycle or combined with ovarian stimulation. IUI with ovarian stimulation improves success rates. Oral ovulatory agents are preferred as first line for ovarian stimulation. It is done usually on Day 12-16 of a cycle when the follicle is mature of 18 mm – 20 mm in size which can be traced either by doing urinary LH home kit or by follicular tracking study by ultrasound. It is done 24 hrs after the positive urinary LH surge or 36 hours – 40 hours after the hcg trigger injection.
Husband gives the semen sample in the laboratory which is washed and centrifuged with culture media which thus concentrates progressively motile sperms, into a small volume. This prepared sample is deposited in the uterine cavity thus close to the site of fertilization. The sperm bypasses the vaginal acidity and has to travel less thus saving its energy for fertilization.
It is a painless procedure carried out in an OPD and does not require anaesthesia.
The intrauterine insemination success rate is upto 20% per cycle. It is recommended that at least 3-4 cycles of treatment are attempted before considering other options.
IUI is absolutely a safe procedure and carries very minimal side effects. There might be cramping at the time of IUI because of the media used for preparation of semen sample in few patients , it subsides on its own after a while. Few cases might require pain killers like crocin or combiflam. There might be psychological impact more so on the male partner, which usually can be addressed by good counselling. The risk of infection is 0.01% – 0.2% of patients which is tackled well with antibiotics. The chances of multiple pregnancy and ovarian hyperstimulation are increased when ovarian stimulation is combined with IUI.
Single IUI done 36 – 42 hours after hcg injection works well . A repeat IUI may have some role in patients with male infertility where repeating IUI 24 hours after the previous one increases the sperm density.
70% – 80% of couples conceive with 4 cycles of IUI. IUI more than six cycles is not recommended.
