Minimal stimulation IVF versus conventional IVF: A Randomized Controlled Trial, Zhang, J et al, Am J OB GYN, 2016

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Dr Daiter’s summary of this research article.
Target: 564 infertile women patients at New Hope Fertility Center from 2009-2013 aged <39 years undergoing their 1st cycle of IVF

Purpose: Compare the reproductive outcomes from one cycle of mini-IVF with single embryo transfer to one cycle of conventional IVF with double embryo transfer

Inclusion criteria included:

(1) women aged 18-38,

(2) normal menstrual cycles,

(3) first IVF treatment, and

(4) infertility diagnosis of male, unexplained or tubal factors

Exclusion criteria included:

(1) pre-existing medical conditions (such as DM, hypertension, hypothyroidism, hyperprolactinemia),

(2) BMI <18.5 or > 32 kg/m2,

(3) day 3 FSH >12 IU/L

(4) submucosal or large intramural fibroids requiring surgery

Pretreatment screening tests included: CBC, varicella and rubella titers, pap smear, syphilis, HIV 1 and 2, hepatitis B, hepatitis C, Chlamydia, Gonorrhea, Prolactin, TSH, CD 3 FSH and E2, baseline ultrasound examination

Mini-IVF protocol:

(1) oral contraceptive pretreatment for 10-14 days with adequate suppression defined as E2 <75 pg/mL,

(2) Clomiphene citrate 50 mg/day started on CD 3 and continued until day prior to triggering,

(3) Gonadotropin COH (Bravelle +/- Menopur; Follistim; or Gonal F) starting on CD 4-7 with 75-150 IU/day,

(3) ovulation trigger with GnRHa (Synarel nasal spray) when lead follicle 18mm diameter,

(4) oocyte retrieval mostly with local anesthesia and follicle flushing as needed,

(5) fertilization by conventional IVF or ICSI as needed,

(6) embryos cultured to blastocyst and vitrified using the CryoTop method (Kitazato Biopharma),

(7) FET with a single embryo in a subsequent natural or artificially prepared cycle with Estrace.

Conventional IVF protocol:

(1) mid-luteal down regulation with Leuprolide acetate,

(2) gonadotropin COH (Bravelle +/- Menopur; Follistim; or Gonal F) on CD 3 with 150-300 IU/day,

(3) HCG (Novarel, Pregnyl, Ovidrel) trigger when at least 2 x 18mm diameter follicles present,

(4) oocyte retrieval with mostly general anesthesia due to large number of follicles to aspirate,

(5) fertilization by conventional IVF or ICSI as needed,

(6) embryos cultured to blastocyst stage,

(7) ET of 2 blastocysts (when available and not medically contraindicated) during the fresh cycle,

(8) vitrification of remaining supernumerary blastocysts for future FET cycles

Conclusion: Mini-IVF with Single Embryo Transfer lowers the live birth rate compared to conventional IVF with 2 embryos transferred (49% compared to 63%) but also significantly reduced the risk of moderate to severe OHSS (0% compared to 6%), reduced the risk of multiple pregnancy (6% compared to 32%), and reduced HMG consumption (459 +/- 131 to 2,079 +/- 389 IU)​

Dr. Daiter’s review of this research article

​Dr. John J. Zhang is a pioneer in Reproductive Endocrinology and Infertility, including but not limited to the field of mini IVF and natural cycle IVF; he founded the very popular New Hope Fertility Center in Manhattan in 2004 and apparently has since opened locations in China, Russia and Mexico; and he is credited with developing the initial protocols for vitrification for cryopreservation in the US, largely based on the work of Dr. Masashige Kuwayama of Japan.

This important article is published in the American Journal of Obstetrics and Gynecology (January 2016), so it is both peer reviewed and current.  It seeks to compare the reproductive outcomes of mini IVF vs conventional IVF in a group of patients with expected “good outcomes” rather than patients with advanced age (study only included women aged 18-38 years), decreased ovarian reserve (excluded women with basal FSH > 12 IU/L), or PCOS (only included women with normal menstrual cycles).

The findings of this study include a statistically significant lower live birth rate when comparing mini IVF with single embryo transfer to conventional IVF with double embryo transfer, but the clinical relevance of this difference (49% to 63%) from the “patient’s point of view” is less certain.  Many patients would prefer mini IVF to conventional IVF since it involves far less medication, most often local as opposed to general anesthesia, virtually no risk of ovarian hyper stimulation syndrome, and a reduced risk of multiple pregnancies.  A candid discussion between physicians and patients to clarify the advantages, disadvantages, and alternatives to mini IVF may result in the identification of a group of patients within the “good outcome” group that would prefer mini IVF over conventional IVF.

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