Follicular versus luteal phase ovarian stimulation during the same menstrual cycle DuoStim in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate New insight in ovarian reserve exploitation

Capsule:
Follicular and luteal phase stimulations show similar in vitro fertilization performance which may lead to a novel strategy to increase the chances of pregnancy in reduced ovarian reserve patient populations.

Authors:
Filippo Maria Ubaldi, M.D., M.Sc., Antonio Capalbo, Ph.D., Alberto Vaiarelli, M.D., Ph.D., Danilo Cimadomo, M.Sc., Silvia Colamaria, M.D., Carlo Alviggi, M.D., Ph.D., Elisabetta Trabucco, M.D., Roberta Venturella, M.D., Gábor Vajta, Ph.D., Laura Rienzi, M.Sc.

Volume 105, Issue 6, Pages 1488-1495

Abstract:

Objective:
To compare the euploid blastocyst formation rates obtained after follicular phase (FP) versus luteal phase (LP) stimulation performed in the same menstrual cycle in a preimplantation genetic diagnosis for aneuploidy testing (PGD-A) program in patients with reduced ovarian reserve.

Design:
Prospective paired noninferiority observational study.

Setting:
Private infertility program.

Patient(s):
Forty-three reduced ovarian reserve patients undergoing a PGD-A.

Intervention(s):
Both FP and LP stimulations using follicle-stimulating hormone and luteinizing hormone in combination with gonadotropin-releasing hormone (GnRH) antagonist starting on day 2 of the cycle and 5 days after the first oocyte retrieval, respectively, where GnRH agonist was used for both FP and LP ovulation triggering; a trophectoderm biopsy quantitative polymerase chain reaction–based PGD-A strategy; and single euploid blastocyst transfers during a subsequent natural cycle.

Main Outcome Measure(s):
Primary outcome measure: euploid blastocyst rate per injected metaphase 2 (MII) oocyte; secondary outcome measures: number of cumulus-oocyte complexes (COCs), MII oocytes, and blastocysts.

Result(s):
Patients with an antimüllerian hormone level of <1.5 ng/mL, antral follicle count of <6 follicles, and/or <5 oocytes retrieved in a previous cycle were included. No statistically significant differences were found in the number of retrieved COCs (5.1 ± 3.4 vs. 5.7 ± 3.3), MII oocytes (3.4 ± 1.9 vs. 4.1 ± 2.5), or biopsied blastocysts per stimulated cycle (1.2 ± 1.2 vs. 1.4 ± 1.7) from FP versus LP stimulation, respectively. No differences were observed in the euploid blastocyst rate calculated either per biopsied blastocyst (46.9% vs. 44.8%) or injected MII oocyte (16.2% vs. 15.0%). Conclusion(s):
Stimulation with an identical protocol in the FP and LP of the same menstrual cycle resulted in a similar number of blastocysts in patients with reduced ovarian response. The LP stimulation statistically significantly contributed to the final transferable blastocyst yield, thus increasing the number of patients undergoing transfer per menstrual cycle.

  • Daniel J. Kaser, MD

    Dear Dr. Ubaldi and colleagues,
    Congratulations on this most interesting follow-up study of Duostim, using a modified Shanghai protocol for separate follicular and luteal phase stimulations and retrievals for poor responders. Has your group ever tried 2-3 days of antagonist immediately following the first retrieval (prior to the second round of gonadotropins) to knock down the corpora lutea?
    Thanks very much for your comments.

  • Godofredo

    I would like to know how they deal when the patient presents multiple ovarian residual hemorrhagic cysts

    • Filippo Ubaldi

      We do not care at the multiple corpora lutea. We just start the luteal stimulation 5 days after the oocyte retrieval. The important thing is to trigger the ovulation with GnRH agonist in order to shorten the demise of the corpora lutea. You will still see corpora lutea at the first ultrasound control on the 5th-6th day of the second stimulation and you have to continue with your stimulation until they will disappear and you will see only the “new” growing follicles.

      Best regards

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