Clinical trial NCT01233206: Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles
Official title: Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Polycystic Ovary Syndrome (PCOS)
Keywords: PCOS
Polycystic ovary syndrome
Cancelled cycles
OHSS
Infertility
Lead sponsor: University Magna Graecia
Sponsor class: OTHER
First posted: 2010-11-03
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins.

Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins.

The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels.

The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.

Detailed description: Infertile young non-obese insulin-resistant patients with PCOS who had a background of the first IVF treatment cycle cancelled because of high risk for OHSS will be enrolled and randomized in two treatment arms.

In their second IVF attempt, the experimental group will receive metformin (500 mg, 3 times daily) pre-treatment for two weeks and co-administration during gonadotropins ovarian stimulation; the control group will be treated with placebo (2 cps daily) pre-treatment and co-administration by using the same schedule of the experimental group. In all patients, ovarian stimulation will be carried out with a personalized step-down gonadotropin in association with a minidose flare-up GnRH agonist protocol.

Eligibility criteria: Inclusion Criteria:

* History of one previous cancelled cycle for high-risk of OHSS, or history of moderate/severe OHSS during their previous IVF cycle
* Infertility
* Polycystic ovary syndrome (PCOS)
* insulin resistance
* hyperandrogenism

Exclusion Criteria:

* BMI\>30 kg/m2
* age \>35 years
* FSH\>9UI/L

Primary outcomes:
measure: Rate of OHSS
timeFrame: one month
Secondary outcomes:
measure: Stimulation length
timeFrame: one month
measure: Gonadotropins dose
timeFrame: one month
measure: Dominant follicles on day of ovulation triggering
timeFrame: one month
measure: Ovulation rate
timeFrame: one month
measure: Peak estradiol levels on day of ovulation triggering
timeFrame: one month
measure: Embryo quality
timeFrame: one month
measure: pregnancy rate
timeFrame: one month
measure: multiple pregnancy rate
timeFrame: one month
measure: Live birth rate
timeFrame: ten months
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Pugliese" Hospital
Study officials:
affiliation: University Magna Graecia
name: Stefano Palomba
role: PRINCIPAL_INVESTIGATOR
affiliation: University Magna Graecia
name: Fulvio Zullo
role: STUDY_CHAIR
References:
citation: Palomba S, Falbo A, Orio F Jr, Manguso F, Russo T, Tolino A, Annamaria C, Dale B, Zullo F. A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination. Hum Reprod. 2005 Oct;20(10):2879-86. doi: 10.1093/humrep/dei130. Epub 2005 Jun 15.
citation: Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Macedo CR. Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD006105. doi: 10.1002/14651858.CD006105.pub4.
citation: Palomba S, Falbo A, Carrillo L, Villani MT, Orio F, Russo T, Di Cello A, Cappiello F, Capasso S, Tolino A, Colao A, Mastrantonio P, La Sala GB, Zullo F, Cittadini E; METformin in High Responder Italian Group. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011 Dec;96(6):1384-1390.e4. doi: 10.1016/j.fertnstert.2011.09.020. Epub 2011 Oct 7.