Effectiveness and Safety Study of Fixed Versus Flexible of Gonadotropin-releasing Hormone Antagonist Protocol

NCT02635607 | Unknown DMC

• 1 other identifier: Merck-IISP-01
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of study is to compare the effectiveness of the Day-5 fixed administration of GnRH antagonist versus flexible administration of GnRH antagonist during ovarian stimulation in Chinese women with predicted high ovarian response, and the hypotheses is that the number of oocyte retrieved in fixed protocol is not inferior to GnRH antagonist flexible protocol.

Conditions

Infertility

Keywords

GnRH antagonist; fixed protocol; flexible protocol

Outcome Measures

Primary Outcomes (1)

• the number of oocytes retrieved

  3 weeks

Secondary Outcomes (6)

• Total dosage of Gn and GnRH antagonist

  3 weeks

• The incidence of premature LH surge during the stimulation

  3 weeks

• The incidence of OHSS during the study

  5 weeks

• The implantation rate

  5 weeks

• clinical pregnancy rate

  6 weeks

Study Arms (2)

Fixed Protocol

OTHER

Patients will start Follitropin beta stimulation on menstrual cycle day 3 and the daily dose will be fixed for the first 5 days of stimulation, a modification of the rFSH dose will be allowed from stimulation day 6 onward. Ganirelix will start fixedly on stimulation Day 5. rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed, and triptorelin trigger will be used as a replacement in case of OHSS high risk

Drug: Follitropin Beta; Drug: Ganirelix; Drug: rhCG; Drug: triptorelin

Flexible protocol

OTHER

Patients will start Follitropin beta stimulation on menstrual cycle day 3 and the daily dose will be fixed for the first 5 days of stimulation, a modification of the rFSH dose will be allowed from stimulation day 6 onward. Ganirelix will start flexibly by the promissory criterion in the flexible group. rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed, and triptorelin trigger will be used as a replacement in case of OHSS high risk

Drug: Follitropin Beta; Drug: Ganirelix; Drug: rhCG; Drug: triptorelin

Interventions

Follitropin Beta DRUG

Patients will start stimulation with a daily s.c. injection of 150IU follitropin beta on menstrual cycle day 3. A modification of the rFSH dose will be allowed from stimulation day 6 onward in case that a high ovarian response occurs at the discretion of the investigator.

Also known as: Puregon

Fixed Protocol; Flexible protocol

Ganirelix DRUG

Ganirelix 0.25mg daily s.c. will start after 4 days of rFSH stimulation

Also known as: Orgalutran

Fixed Protocol

rhCG DRUG

An amount of 250ug rhCG will be administered to induce final oocyte maturation as soon as at least three follicles of ≥17 mm were observed

Also known as: Ovidrel

Fixed Protocol; Flexible protocol

triptorelin DRUG

0.2mg triptorelin will replace rHCG to trigger in case of high risk of overstimulation

Also known as: Decapeptyl

Fixed Protocol; Flexible protocol

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Have an indication for COS and IVF/ICSI;
• be \<35 years old;
• have a BMI of 18-25kg/m2;
• have a regular menstruation with a range of 24-35 days;
• fulfill one of these three criteria as follow:
• the number of oocytes retrieved\>15 in previous COS cycle;
• Serum AMH (examined on the menstrual cycle day 2)\>3.52ng/ml;
• antral follicle count (AFC) (examined by ultrasonic on the menstrual cycle day 2)\>16
• have willingness to give informed consent

You may not qualify if:

• Presence of unilateral ovary absence;
• Any difficulty on oocyte pick-up with abnormal condition of ovary and pelvic cavity;
• Women have any clinically relevant pathology could impair embryo implantation or pregnancy continuation (uterine malformation, intermural uterine fibroids\>3cm, intrauterine adhesion,etc);
• Women with polycystic ovary syndrome (PCOS) diagnosed by Rotterdam consensus criterion(Rotterdam, 2004)
• Other known abnormal ovulation disorders (including but not limited to adrenal gland disease, thyroid disease and hyperprolactinemia);
• A history of recurrent miscarriage or previous IVF cycles failure\>2;
• A history of ovarian hypo-response in previous ovarian stimulation;
• Women with other clinical/socio-economic factors precluding the completion of the study at the discretion of the investigator.

Sponsors & Collaborators

• Chong Qing Reproducive and Genetic Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Related Publications (7)

• Humaidan P, Quartarolo J, Papanikolaou EG. Preventing ovarian hyperstimulation syndrome: guidance for the clinician. Fertil Steril. 2010 Jul;94(2):389-400. doi: 10.1016/j.fertnstert.2010.03.028. Epub 2010 Apr 22.

  PMID: 20416867 BACKGROUND

• Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, Abou-Setta AM. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011 May 11;(5):CD001750. doi: 10.1002/14651858.CD001750.pub3.

  PMID: 21563131 BACKGROUND

• Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Alexopoulou E, Kolibianakis EM. Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT). Hum Reprod. 2010 Mar;25(3):683-9. doi: 10.1093/humrep/dep436. Epub 2009 Dec 15.

  PMID: 20008886 BACKGROUND

• Al-Inany H, Aboulghar MA, Mansour RT, Serour GI. Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible protocol. Reprod Biomed Online. 2005 May;10(5):567-70. doi: 10.1016/s1472-6483(10)61661-6.

  PMID: 15949209 BACKGROUND

• Hamdine O, Eijkemans MJ, Lentjes EW, Torrance HL, Macklon NS, Fauser BC, Broekmans FJ. Ovarian response prediction in GnRH antagonist treatment for IVF using anti-Mullerian hormone. Hum Reprod. 2015 Jan;30(1):170-8. doi: 10.1093/humrep/deu266. Epub 2014 Oct 29.

  PMID: 25355590 BACKGROUND

• Engmann L, DiLuigi A, Schmidt D, Nulsen J, Maier D, Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil Steril. 2008 Jan;89(1):84-91. doi: 10.1016/j.fertnstert.2007.02.002. Epub 2007 Apr 26.

  PMID: 17462639 BACKGROUND

• Luo X, Pei L, Li F, Li C, Huang G, Ye H. Fixed versus flexible antagonist protocol in women with predicted high ovarian response except PCOS: a randomized controlled trial. BMC Pregnancy Childbirth. 2021 May 2;21(1):348. doi: 10.1186/s12884-021-03833-2.

  PMID: 33934703 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

follitropin beta; ganirelix; Ovidrel; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Hong Ye, bachelor

  Genetic and Reproductive Institute, Chongqing Obstetrics and Gynecology Hospital

  STUDY DIRECTOR

Central Study Contacts

Xiu Luo, master

CONTACT

008602363839850; luoxiu1982@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 21, 2015
• Study Start: January 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: March 1, 2017
• Last Updated: December 21, 2015

Record last verified: 2015-12