DR. INDIRA GANESHAN IS A FRAUD VISIT WWW.SURROGACYNEEDS.COM

Treatment


Treatment of an infertile couple should be holistic in nature; once the basic tests are done and the diagnosis clinched, this would give us the line of treatment which the patient would benefit from. The treatment can be medical, surgical and psychological therapy. Infertility and fertility therapy can be extremely stressful for the patients, apart from the stress of the investigation and treatment, patient has to go through social and family pressure. A couple should have adequate and trained counselors to help them cope with the pressure of investigation and infertility treatment .This counseling session of the stressed out patient not only help the patient to have a focused and positive outlook to the whole process it also prevent the drop out rates.



Treatment of the female partner


Treatment of the female partner is   more difficult, expensive, extensive, time consuming process with limited success. The first step in the treatment of infertile couple is finding out if the couple is aware of fertile period. Treatment would start with explaining patient about fertile period followed by life style modification, achieving ideal body weight and stress reduction. This would be followed by control of any endocrine disturbance like diabetes, hyperprolactinemia or thyroid disorder.



Hyperprolactinemia

The causes of hyperprolactinemia are discussed in the other chapter. The treatment would start with identifying the cause and the extent of the disturbance (Galactorrhoea, amenorrhoea, infertility). The drug induced hyperprolactinemia can be reversed by stopping or substitution of the causative drug. Treatment of causative problems like with hypothyroidism will restore normal prolactin level.

Medical management
is by two drugs, namely Bromocriptine and Cabergolin they are dopamine agonist.

Bromocriptine is started at the dose of 1.25mg or half tablet of standard available strength of 2.5mg,taken with meal at night and slowly escalated to 2.5mg till the normal level are achieved. Bromocriptine is not well tolerated by patients because of side effects. Alternatively Bromocriptine tablets can be used intravaginally and this has better tolerance. It may take 6-10weeks for the control of the prolactin levels, then the dose should be reduced to lower maintenance dose. Bromocriptine seems to be safe in pregnancy, inspite of that it is recommended that the therapy be discontinued when the women conceives.
Side effects of low dose Bromocriptine
  • Nausea
  • Vomiting
  • Constipation
  • Headache
  • Dizziness
  • Postural hypotension
  • drowsiness
Cabergolin
Cabergoline an ergot derivative, is a potent dopamin receptor agonist. It also acts on dopamine receptors in lactophilic cells in hypothalamus to supress prolactin production in the pitutarygland.the main advantage of cabergolin is the lower side effect and flexibility of weekly or biweekly dosage.The starting dose is 0.25mg twice a week and after the normalisation of prolactin level ,the dose can be lowered to maintanence dose.
Side effect is same as bromocriptine.
Ovarian induction
Insulin sensitizers
  1. Metformin
  2. Traglitazone (Now banned)
  3. Rosiglitazone (only in patients not wanting a pregnancy)
  4. Pioglitazone – under trial
Medical methods for augmentation of ovulation 
  1. Metformin
  2. Clomiphene citrate(CC)
  3. Letoval
  4. Gonadotrophin releasing hormone
  5. Gonadotrophins
  6. Pure FSH
  7. HMG
Metformin is a biguanide, available in strength of 500 or 850 mg, recommended dose is around 1500-2000mg in divided doses.
Metformin has been shown to reverse the endocrine abnormalities seen with PCOS within 2 or 3 months. They can result in diminished facial and body hair growth, regulations of menstrual flow, weight loss and spontaneous ovulation.
Patients need to be started on Metformin in a low dose and then gradually increased to the required doses as they might experience side effects like giddiness, gastro intestinal like diarrhea, cramps, nausea, vomiting, flatulence, indigestion, abdominal discomfort. In 10-30% cases it causes malabsorption of vitamin B 12, these side affects can be minimized by taking Metformin with meal.
Treatment with rosiglitazone can only be given in patients who are not trying for pregnancy. It is a well tolerated alternative for over weight PCOS patients; it helps in improving menstrual cyclicity, hyperandrogenism, insulin resistance in hyperinsulinaemic patients.
Clomiphene citrate
Mechanism of action of CC

CC is an estrogen receptor modulator. It binds to the hypothalamus, thus preventing the usual negative feedback of estrogen on GnRH during the follicular phase. This results in increased FSH stimulation to the ovary from pituitary. major problem with CC is that it can bind to the estrogen receptor for an extended period of 6-8weeks and depletes estrogen receptor in estrogen dependent tissues like cervix and endometrium, which affects the endometrial development and causes, decreased cervical mucus production.
CC: Very popular agent for the induction of ovulation and has been in use for around 40 years. 50gm is the starting dose to be started on day 2 or day 3for better recruitment of follicles. This is followed by follicular study using Ultrasonography from Day9, till collapse of follicle to suggest ovulation. If the response is poor, the dose can be increased in subsequent cycle. A maximum of 4-6cycle is recommended.
Side effects of CC
  1. Visual disturbance
  2. Ovarian hyperstimulation
  3. Hot flushes
  4. Abdominal discomfort
  5. Nausea
  6. Vomiting
  7. Depression
  8. Insomnia
  9. Breast tenderness
  10. Weight gain
  11. Rash
  12. Dizzness and hair loss.
CC is contraindicated in
  1. Liver disorder
  2. Ovarian cyst
  3. Endometrial cancer
  4. Uterine bleeding
Letrozole

Aromatase inhibitors are primarily used in the management of postmenopausal breast cancer. Their use in ovulation induction is because of their ability to inhibit androgen to estrogen conversion, thus lowering the estradiol levels. The low level of estradiol causes the reduction in negative feedback and thus increase pituitary gonadotropin output, leading to ovulation induction. when the follicles starts developing and subsequent estradiol level starts increasing,FSH levels decrease by feedback effect on HPO, as the hypothalamic estrogen receptors are not blocked.
Dosage 2.5mg to 5mg once a day for 5 days, it has a very short half life so unlike CC does not cause luteal phase problems and is well tolerated.
GnRH

Increased doses of GnRHmay be used effectively for ovulation induction in some patientswith GnRH receptor mutations. Pulsatile administration of GnRH by the subcutaneous pump as administered in hypogonadotrophichypogonadism patient, helps in folliculogenesis and with administration of hCG causes the release of oocyte for achieving pregnancy. A higher dose of GnRH is requiredfor normal luteal phase dynamics than for normal follicularphase function.
Gonadotrophins in PCOS

For patients who have PCOS, who are not responsive to weight loss, Metformin, CC, Letoval or ovarian drilling the next step would be injectable gonadotrophins. The critical component in such preparation is FSH (recombinant FSH or highly purified urinary FSH and never hMG as it has LH and FSH) .The regimen for induction of ovulation in PCOS patient has to take into account the age, weight and any past history of hyperstimulation of ovaries . The protocol for stimulation will also depend on whether the patient is scheduled for natural cycle/IUI/IVF/ICSI.
If the patient is for natural cycle or IUI, patient is started on CC(50mg) or Letoval(2.5/5mg) from day 2 ,once a day for 5days and  Ultrasound is performed on day 7 to assess the number and size of the recruited follicle, and addition of gonadotrophins can be done from day 7 daily or alternate day depending on the response.
Pure FSH injection can be given daily from day2, starting with half ampoule of 75unit (37) with serial monitoring with transvaginal USG, The dose is adjusted according to ultrasound or serum estradiol level (step up protocol) depending on the response and when follicular size reaches 18mm ovulation trigger can be given with injection hCG followed by a timed contact or IUI. While stimulating patients of PCOD one has to watch out for development of OHSS.

Hypogonadotropichypogonadism


The treatment of Hypogonadotropichypogonadism is hormone replacement therapy. This can be done in pulsatile continuous manner using a subcutaneous GnRH pump, which can be programme to delivery different volumes of drug various interval. The pulsatile administration of GnRH makes the pituitary   to produce FSH & LH. This acts on the ovaries to producer follicular development and estrogen and progesterone monitoring is done by USG.
Or we can give daily injections of FSH for stimulating the ovaries to produce the follicle, which is monitored by Ultrasound and estradiole level.
The use of pulsatile GnRH is highly effective and large percentage of female with hypogonadotrophichypogonadism ovulate and subsequently get pregnant of there is no male factor

Surgical method for ovulation induction
Ovarian drilling

In PCOS patients who are resistant to injectable gonadotropin treatment, laparoscopic ovarian drilling is next step. It involves the use of unipolar cautery for making2-4 holes per ovary. The detail of the procedure is covered in a separate chapter.
The benefits of drilling are
  1. Marked decrease in androstenedione
  2. Decrease in testosterone levels
  3. Increase in spontaneous ovulation and pregnancy rates
  4. Decrease in spontaneous miscarriage
  5. Fall in multiple pregnancy risk