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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental group | Experimental | Patients receiving metformin pretreatment and co-administration |
|
| Control group | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Metformin pre-treatment and co-administration |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of OHSS | one month |
| Measure | Description | Time Frame |
|---|---|---|
| Stimulation length | one month | |
| Gonadotropins dose | one month | |
| Dominant follicles on day of ovulation triggering |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stefano Palomba | University Magna Graecia | Principal Investigator |
| Fulvio Zullo | University Magna Graecia | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pugliese" Hospital | Catanzaro | 88100 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15958399 | Background | 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. | |
| 33347618 |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| D011085 | Polycystic Ovary Syndrome |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Placebo administration |
| Drug |
Placebo pre-treatment and co-administration |
|
| one month |
| Ovulation rate | one month |
| Peak estradiol levels on day of ovulation triggering | one month |
| Embryo quality | one month |
| pregnancy rate | one month |
| multiple pregnancy rate | one month |
| Live birth rate | ten months |
| Derived |
| 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. |
| 21982727 | Derived | 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. |
| D009369 |
| Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |