Minimal ovarian stimulation combined with elective single embryo transfer policy

Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort Kato, K et al.  Reprod Biol Endocrinol 2012

Dr Daiter’s summary of this research article
Target:  A retrospective cohort study at Kato Ladies Clinic involving 7,244 patients and 20,244 IVF cycles with clomiphene citrate based minimal stimulation or natural cycle IVF protocols during 2008

Purpose: To evaluate the embryological and clinical results of a large exclusively single embryo transfer program according to patient age (<30, 30-34, 35-39, 40-44, >44)

Protocol: The clomiphene based minimal stimulation method is described in other articles and for the natural cycle IVF protocol the only medication used was to trigger ovulation with a GnRH agonist.  The natural cycle protocol included:

  1. Ultrasound and serum blood work (E2, LH, Progesterone) monitoring starting on day 10 and/or 12 (based on patient’s cycle length)
  2. Triggering ovulation when the lead follicle reached 18mm with an E2 >250 pg/mL
  3. Egg retrieval 30-34 hours after triggering ovulation unless an LH surge was detected on serum blood work and then egg retrieval was set for 20-30 hours later.
  4. Single embryo transfer was performed using fresh cleavage stage embryos on day 2-3 about half the time and the remaining half the time the embryos were cultured to blastocyst stage and vitrified for subsequent frozen thaw blastocyst transfer cycles.

A total of 20,244 IVF cycles were initiated, the mean age of the patient was 39 (range 22-53), the average number of eggs retrieved was 1.5, no significant differences were observed in the proportion of successful retrievals (78%) according to different age groups except a significantly reduced rate for women >45 years old, fertilization (80%) and cleavage rates (91%) were not significantly different between age groups, blastocyst formation (70% to 23%) and live birth rates (36 to 2%) did show a significant decrease dependent on age, and frozen thawed blastocyst transfer cycles gave the highest chance of live birth per embryo transfer (41 to 6%).

Conclusion: High fertilization and cleavage rates were obtained regardless of age, whereas blastocyst formation and live birth rates demonstrated an age dependent decrease.  The elective single embryo transfer program based on this minimal ovarian stimulation protocol provides reasonable live birth rates per embryo transfer for women up until their mid-forties.  In women aged 45 and above the success rates drop dramatically to less than 1%.

Dr. Daiter’s review of this research article

The Kato Ladies Clinic in Japan is one of the largest IVF centers in the world and it focuses its treatment protocols on natural cycle and minimal stimulation IVF

Experience with over 20,000 IVF cycles suggests that when natural cycles are used (only using medication to trigger ovulation once a mature follicle is identified) there are age related pregnancy and live birth rates that are reasonable for women up to their mid forties.​

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