Ovulation induction with pulsatile gonadotrophin releasing
hormone (GnRH)
by Strahimir Banovic, MD, OBGYN.net
International Representative - Croatia
Specialist Gynaecologist And Obstetrician
O&G Practice, Zagreb, Srednjaci B.B.
Introduction:
ANOVULATORY INFERTILITY has been successfully treated in 7 out of 13 women by means of pulsatile gonadotrophin releasing hormone (GnRH) therapy. Women with primary or secondary amenorrhoea received a bolus of GnRH (2,1 - 20 m g) subcutaneously once every 60, 90 or 120 min around the clock from a programmable battery operate, syringe driver worn under the clothing. Duration of treatment varied from 1 week to 8 months (mean 2,5 months). 7 women ovulated and 2 conceived in the first months of treatment. We conclude that anovulatory women with normal Prolactin levels, who are refractory to clomiphene with or without HCG, and who are unlikely to respond to anything but human pituitary FSH and HCG may now be treated with GnRH.
Materials And Methods:
Disorders of ovulation are conditions in which ovulation does not occur or/and is inadequate for conception. The sequelae are serious and include increase rate of psychological complication and most importantly, infertility.
Hormonal therapies employing GnRH generally have better prognosis in terms of fertility.
The treatment of infertility has priority in our country.
It has proved to be a safe economical, and efficient means of therapy which can be used in women of reproductive age.
We postulate that conception is influenced by the ratio between estrogen (E2) and progesterone (P), which are dependent on the plasma circulating levels of gonadotrophins (FSH, LH) and (GnRH) themselves dependent on the secretion of gonadotrophins releasing hormone.
Pulsatile GnRH therapy is an effective means of treating gonadotrophin deficiency. if it is due to hypothalamic dysfunction.
We are examining fertility of women who have had surgical correction and other therapies for ovulation induction, hereto unsuccessfully.
We do use the Zyklomat pulse driver which motor is activated for 3 min each 60 min. The GnRH was delivered from a 2 ml syringe containing 100 m g of GnRH / ml through 27 gauge scalp vein needle to a subcutaneous site on the anterior abdominal wall. Subsequently we used a Portex epidural catheter (Code No 100/380/200) inserted 9 cm subcutaneously in the lower abdominal wall. A balus of 3,25 micg GnRH in solution was delivered over 3 min at hourly intervals.
Hypothalamic anulatory infertility will be treated by means of pulsatile administration f gonadotrophin releasing hormone (GnRH). In women lacking endogenous GnRH will initiate normal ovulation and menstruation. In the group of women who fail to ovulate with clomiphene there is a spectrum of hypothalamic dysfunction that same ovulate with various doses of GnRH.
Thirteen anovulatory women refractory to Clomiphene, were given 80-300 micg GnRH / day. Seven of the ten women who ovulated did so in the first month and five of the ten conceived with singleton pregnancies. Three women conceived in the first cycle, one in the second, and one in the fourth cycle.
Conclusion:
We hope that GnRH administered in a pulsatile fashion every 1-2 h. subcutaneously will induce ovulation in women with anovulatory infertility unlikely to respond to anything but HPFSH/HCG.
Research is in the conformance to Croatian legislation and international conventions.
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Table #9 Summary of the pre-treatment clinical data |
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| Patient no. |
Age (years) | Duration of amenorrhea | Duration of infertility | Diagnosis | Clomiphene/MPA test | Comments |
| 1 1a |
29 32 |
1*Am | 3 years | Congenital GnRH deficiency | -ve/-ve | 2 ´ Conception and abortion on hFSH/hCG ovarian hyperstimulation |
| 2 | 28 | Oligo | 30 months | PCO | -ve/ND | Obese, hirsute, conceived first child on hFSH/hCG |
| 3 | 25 | 5 years | 3 years | 2° HA | -ve/+ve | |
| 4 | 27 | 2 years | 2 years | 2° HA | -ve/-ve | Previus anorexia nervosa weight = 50.3 kg |
| 5 | 25 | 1*Am | Congenital GnRH deficiency | ND/ND | ||
| 6 | 30 | 11 years | 3 years | 2° HA | nd/nd | Athlete |
| 7 | 35 | 5 years | 4 months | 2° HA | nd/nd | Athlete |
| 8 | 29 | 4 years | 21 months | 2° HA | -ve/+ve | |
| 9 | 33 | 17 months | 17 months | 2° HA | -ve/ND | |
| 10 | 27 | 1*Am | 1° HA | -ve/ND | ||
| 11 | 25 | Oligo | 4 years | 2° HA | ND/ND | |
| 12 | 23 | 18 months | 18 months | pco | -ve/ND | |
| 13 | 27 | 1*Am | 2 years | 1° HA | -ve/+ve | |
| Oligo - oligomenorrhoea. 1*AM - primary amenorrhea. PCo - ploycystic ovarian disease. 2° HA - secondary hypotalamic amenorrhoea. MPA - medroxy progesterone acetate. ND - test non done. | ||||||