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PCOS and IVF: A Comparison Between Standard Long Protocol Versus an Antagonist Protocol Starting on Day 1

18 Years
37 Years
Not Enrolling
Polycystic Ovary Syndrome, In Vitro Fertilization

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Trial Information

PCOS and IVF: A Comparison Between Standard Long Protocol Versus an Antagonist Protocol Starting on Day 1

Hejinen et al (1) recently conducted a meta-analysis to compare outcomes of conventional IVF
in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. They
compared nine RCTs reporting data on 458 PCOS patients (793 cycles) and 694 matched controls
(1116 cycles) and concluded that in PCOS there is an increased cancellation rate, but more
oocytes retrieved per pick-up and a lower fertilization rate. Overall, PCOS and control
patients achieved similar pregnancy and live birth rates per cycle. The incidence of ovarian
hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported.

Our results are in accordance with this meta-analysis. Therefore, if the pregnancy and
abortion rates in PCOS and controls do not differ, the main problem when dealing with PCOS
in IVF is OHSS. This condition can be approached by using an antagonist instead of an
agonist, by changing the kind of ovulation trigger and by co-treating patients with

- One of the currently debatable issues regarding the use of GnRH antagonists refers to
the timing of GnRH antagonist initiation. A fixed protocol starting antagonist
arbitrarily on Day 6 of stimulation has been used in all introductory comparative
trials employing a daily antagonist administration (2). Following these trials, a
flexible antagonist initiation by a follicle of 14-15 mm has been evaluated. Currently,
initiation of antagonist in the early follicular phase in PCOS patients has been
performed by Lainas and coll. (3) who treated patients with PCOS either with a long
GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol and concluded that
initiation of GnRH antagonist concomitantly with recombinant FSH on day 1 is associated
with an earlier follicular growth and a different hormonal environment during the
follicular phase when compared with the long agonist protocol. This may lead to a
reduction in the incidence of OHSS.

- Over the past 15 years, it has become increasingly recognized that insulin resistance
is central to the pathogenesis of the PCOS (4). Metformin, a biguanide insulin-lowering
agent, has been extensively investigated in the management of PCOS. Two recent
systematic reviews (5, 6) demonstrated that metformin improves reproductive function of
some women with PCOS. Metformin also appeared to improve the outcomes of ovulation
induction therapies when combined with clomiphene and gonadotrophin. Tang et al.
recently studied PCOS overweight patients undergoing IVF to whom they administered 850
mg bid or placebo 28 days prior to the stimulation (7). They concluded that short-term
co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not
improve the response to stimulation but significantly improves the pregnancy outcome
and reduces the risk of OHSS.

The aim of this study is to verify if using an antagonist the number and quality of MII
oocytes is equal compared to a standard long agonist protocol while reducing the risk of

Outcome measures:

Primary endpoints:

- Oocytes MII Secondary endpoints

- Fertilization rates

- Pregnancy rates

- Miscarriage rates

- Incidence of OHSS

Inclusion Criteria:

- PCOS patients according to the Rotterdam consensus criteria

- Presence of both ovaries

- Absence of endometriomas detected at ultrasound

- FSH < 10 IU/L on day 3 of the cycle

- E2 < 80 pg/mL, and Pg < 1.6 ng/mL at initiation of stimulation

Exclusion Criteria:

- Congenital adrenal hyperplasia

- Cushing's syndrome

- Androgen-producing tumours

- Hyperprolactinaemia and thyroid dysfunction

- Age > 38 years

- Serum FSH levels > 10 mIU/ml

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Oocytes MII retrieved per patient

Outcome Time Frame:

1 Day

Safety Issue:


Principal Investigator

Fulvia Mancini, M.D. PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Obstetric, Gynecology and Reproductive Medicine


Spain: Ethics Committee

Study ID:




Start Date:

April 2009

Completion Date:

June 2012

Related Keywords:

  • Polycystic Ovary Syndrome
  • In Vitro Fertilization
  • Polycystic Ovary Syndrome
  • GnRH Antagonist
  • Long Agonist Protocol
  • OHSS
  • Polycystic Ovary Syndrome