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

Modified Natural Cycle IVF

CUMULATIVE PREGNANCY RATE AFTER MODIFIED NATURAL CYCLE IVF (MNC-IVF)

(2001-2005 study by the University Medical Center of Groningen, Netherlands;
Pelinck, MJ et al, Human Reproduction, Vol. 22, No. 9, pp 2463-2470, published June 2007)

Treatment is aimed at using the one follicle that spontaneously develops to dominance in a natural cycle, using a GnRH antagonist (0.25 mg daily) with gonadotropin (Gonal-F 150IU [2 vials]  daily) in the late follicular phase only.

In this single-center study, nine cycles of MNC-IVF were offered to 268 patients, aged 18-36, with regular ovulatory menstrual cycles of 26-35 days.  Treatments were performed in consecutive menstrual cycles, unless the patient requested otherwise.
Excluded from the study were patients who had an endometrioma at the time of screening, and patients requiring ICSI because of severe male factor.

Cumulative pregnancy rates (CPRs) were calculated, and  drop-out was analyzed.

Results:
1. 256 patients completed 1048 cycles (average 4.1 per patient).
2. Embryo transfer rate – 36.5% per started cycle
3. Ongoing pregnancy rate – 7.9% per started cycle, 20.7% per embryo transfer.
4. CPR after up to 9 cycles was 40.6%.
5. Drop-out rate – 47.8% of patients left the program before conceiving or before completing 9 cycles.
6.  Cancellation of oocyte retrieval, fertilization failure and failure to reach embryo transfer were repeating phenomena in     
     cycles for the same patients, and these events predispose to drop-out.
7. Reasons for cancellation were premature LH rise or ovulation before antagonist could be started. (46 cycles), lack of
    follicle development or difficult visualization of the ovaries (28 cycles), ovarian cysts not resolving spontaneously (6 cycles),
    illness or personal reasons (12 cycles), insufficient sperm for conventional IVF (1 cycle).
8. Pregnancy rate per cycle did not decline with more cycles, possibly due to selective dropout of poor-prognosis patients.
9. Pregnancy rate per cycle and CPR per patient were not different according to diagnosis (reason for IVF).

Conclusion:
Due to the low risk and patient-friendly nature of MNC-IVF, it seems a feasible treatment option for patients requiring IVF.

Modified Natural Cycle IVF

EMBRYO QUALITY IN NATURAL VS STIMULATED IVF

[2004 study by a University Hospital in Denmark;
S. Ziebe et al, Human Reproduction, Vol. 19, No, 6, pp. 1457-1460, published April 22, 2004]

This was studied in the same women who had undergone both modified natural-cycle IVF and standard-dose stimulated IVF..

Conclusions:

1. Use of hormonal stimulation does not alter the ability of the oocyte to cleave after fertilization.
2. The developmental capacity of the embryo – defined as the number of blastomeres after two days of culture – is also unaffected .

3. Embryo quality in terms of degree of fragmentation is similar in both natural and stimulated cycles.

Modified Natural Cycle IVF

MODIFIED NCIVF (MNC-IVF) NOT REALISTIC FOR POOR RESPONDERS WITH HIGH DAY-3 LEVELS

[2001-2003 study by the Fertility Center of the Free University of  Brussles;
Kolibiniakis et al, Human Reproduction, Vol. 19, No. 11, pp 2545-2549, published Oct. 7, 2004]

Patients studied:  Women with FSH >12 on D3 of cycle, with five or less oocytes retrieved in a previous standard IVF.

Protocol: Gonal-F (recombinant FSH)+antagonist  started when follicle reached mean diameter of 14mm; 10000IU HCG given when follicle reached >16mm, regardless of estrogen level reached. Hormonal evaluation for Estradiol/lH/FSH was started on Day 8 .

Results:

1. 25/78 (32.1%) did not result in oocyte retrieval.
2. In 9/53 (16.9%) cycles in which retrieval was done,  no oocytes were retrieved.
3. Embryo Transfer was performed in only 19 out of 44 cycles (43.2%) where oocytes were retrieved.
4. No ongoing pregnancy was achieved.

Modified Natural Cycle IVF

MODIFIED NATURAL-CYCLE IVF
[2002-2003 study by European Hospital, Rome, and University of Naples;
Ubaldi, F. et al, Annals New York Academy of Sciences 1034: 245-251(2004)]

Patients: Severe male-factor with previous IVF cancellations D/T failure to obtain >2 oocytes.
Protocol: Same as Brussels study.

Results:
PR/cycle                  35/258 (12.5%)
PR/patient               35/157 (22.2%)
PR/ET                     35/133 (26.3%)
IR                          37/135 (27.4%)
SPAB rate                  8/35 (22.8%)

Modified Natural Cycle IVF

CUMULATIVE PREGNANCY RATES AFTER 3 CYCLES OF MINIMAL-STIM IVF

[Multi-center cohort study in the Netherlands Jan 2001-2005;
Pelinck, MJ et al, Human Reproduction, Vol. 21, No. 9, pp 2375-2383, published June 3, 2006)

NB: This study uses the term ‘minimal stimulation IVF’ for what is generally called ‘modified natural cycle IVF (MNC-IVF)
in which

1. GnRH antagonist (0.25 mg) used in late follicular phase to prevent untimely LH surge
2. FSH  (150 IU) given to substitute for the expected fall in Estradiol
3. HCG  (5000 IU) given 32-36 horus before egg retrieval to ensure follicle amturation

Results:
336 patients underwent 844 cycles.
Ongoing PR/cycle started   8.3%
Cumulative ongoing PR after up to 3 cycles 20.8%  
No differences found according to diagnosis.
CONCLUSION: MNC-IVF seems suitable for all indications studied.
ADVANTAGE: No resting cycle needed – treatments can be repeated in consecutive cycles.

Modified Natural Cycle IVF

CUMULATIVE PREGNANCY RATE AFTER MNC-IVF

[2005 Netherlands study.  Pelink MJ, Human Reproduction 2005; 20:642-648]

NB: This is the study that was extended to 9 cycles in the  preceding article.

356 patient cycles  were studied, using the same protocol described above.

Results:
Pregnancy rate 20% per embryo transfer
Cumulative PR after up to 9 cycles 44%, with  no decline even with more cycles.