NATURAL CYCLE IVF

The following is a summary presentation of recommended recent articles in medical journals

MNC-IVF USING GnRH ANTAGONIST CAN BE AN OPTIONAL TREATMENT IN POOR RESPONDERS

[Jan. 2001-Oct. 2002 study by two Israeli centers,
Journal of Assisted Reproduction and Genetics, Vol. 22, No, 2, Feb. 2005, pp 75-79]

Retrospective study of 540 cycles of patients with a history of poor response to stimulation.  They were divided into three groups by treatment protocol:

1. MNC-IVF (52 cycles) – Antagonist (Cetrotide 0.25 mg) + 2-3 ampules HMG (Menogon, similar to Pergonal) started when dominant follicle was 13mm
2. Standard IVF, antagonist protocol  (200 cycles) – Menogon or Gonal-F at minimum 225 IU(3 vials) a day started on Day 2; Cetrotide 0.25 mg. started daily when dominant follicle reached 13mm.
3. Standard IVF, long agonist protocol –  Single-dose Lupron depot started on Day 231 of the previous cycle;

Stimulation with Menogon or Gonal-F  at minimum 225 IU (3 vials) dailystarted 15 days after verificationof complete ovarian suppression.

All patients underwent baseline hormonal evaluation and transvaginal ultrasound. Estradiol, LH and progesterone levels were
monitored until a follicle reached 18mm. Oocytre retrieval took place 32-36 hours after HCG administration.

Results:

1. Mean number of oocytes retrieved in the MNC group was significantly lower than in the stimulated groups (1.4+/- 0.5 vs,. 2.3+/- 1.1 in the antagonist group,  and 2.5 +/- 1.1 in the long agonist group.
2. The respective implantation and pregnancy rates were:
   
   a.  MNC-IVF                 10%,    14.3%                        
   b. Antagonist                6.75%, 10.2%
   c. Long agonist             7.4%,   10.6%
   
   There was no statistically significant difference in these rates – which means, cycle outcome and proerties were similar for all three treatment protocols, except in cancellation rates.

3. Cancellation rates for the three groups were 32.6%, 17%, and 18.4%, respectively The cancellation rate for the

MNC group was considerably higher,  but  most of the cancellations (q13.5%) was in patients older than 40, and was due to failure of ovarian response, not to premature LH surge. (A 2002 review of  natural-cycle results reported up to 2002 showed that the cancellation rate in natural cycles ranged from 14.3-62.5%

Natural Cycle IVF
NC-IVF AS A  FIRST APPROACH IN ELDER PATIENTS WITH ELEVATED FSH
 [2005 study at San Raffaele University Hospital, Milan;
Papale, E et al, Gynecological Endocrinology, July 2006; 22(7): 351-354]

9-24% of all patients undergoing stimulation for IVF are poor responders. Poor responders are generally identified by previous failure of a standard IVF as a consequence of too few

1. follicles recruited
2. oocytes collected
3. embryos transferred

Diminished ovarian reserve (DOR)  is the main reason for poor response in this patients.
Increased baseline FSH (>10-12) is inversely correlated with ovarian reserve and responsiveness to treatment. – i.e., the higher the FSH, the lower is the patient’s ovarian reserve and patient’s responsiveness to treatment.

Recently, antral follicle count has been used to predict ovarian response in patients undergoing standard IVF. These are follicles visible on ultrasound (>4-5 mm in diameter) during the first few days of the menstrual cycle.  Except for patients with polycystic ovaries, who chronically have several antral-size follicles, more antral follicles seen at this time usually means the patient has a better ovarian reserve, will generally be more responsive, and therefore, have a better chance to conceive with treatment.

Normally, there is a marked increase of follicular depletion from the age of 37-38. Age-related oocyte quality decreased in parallel to progressive follicle loss.  The combination of decreased quality and number of oocytes explains declining fecundity in females.

Better embryo quality (as a result of natural oocyte selection), better endometrial receptivity, and  the monthly repeatability of the procedure can balance the relatively low chance of proceeding to embryo transfer in NC-IVF.

In this study:
Overall pregnancy rate – 11.5% per cycle, 20% per embryo transfer – was comparable to conventional IVF in aged patients.