Efficacy and Safety of Medication Used to Stimulate Ovulation

NCT02715336 | Unknown Phase 4

• 1 other identifier: CFC-01
• Study Type: interventional
• Target: 666
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals undergoing In Vitro Fertilization must undergo controlled ovarian hyperstimulation (COH) to produce enough quality eggs for fertility treatment. Ovarian follicular responsiveness to COH with gonadotropins is extremely variable between patients and even from cycle to cycle for the same patient. Achieving an ideal follicular response is critical to the success of assisted reproduction treatment (ART). Patients have been classified as 'poor', 'normal' or 'high' responders, which dictate the amount of gonadotropins that they receive. It is still important to develop treatments with high efficacy, lower multiple birth rates, and a lower complication rate for each of these groups. In an era of evidence-based medicine and with special emphasis on reducing IVF risks (mainly OHSS and pregnancies with multiples), it is very important to find optimal and safe ovulation induction and triggering regimens for each patient population. The use of GnRH agonist (GnRHa) triggering among high responders in order to reduce or eliminate OHSS is an example of an important breakthrough in the clinical management of IVF patients. Although GnRHa triggering was shown to be as effective as human chorionic gonadotropin (hCG) at inducing oocyte maturation more than 20 years ago, its use to trigger ovulation was not possible until the introduction of GnRH antagonists for pituitary suppression. Another prominent trend in ART in recent years has been the introduction of dual triggering, which involves a combination of GnRHa plus hCG for triggering. This regimen creates simultaneous lutenizing hormone (LH) and follicle stimulating hormone (FSH) surges by the GnRHa, which resembles physiologic ovulation triggering, together with sustained LH-like activity from the hCG, which stimulates the corpus luteum to excrete sufficient hormonal endometrial support. Since its introduction, dual triggering has been gaining popularity due to outstanding results in retrospective studies among both normal and high responders. Moreover, in spite of the encouraging retrospective reports, prospective randomized controlled trials (RCT) on dual triggering have not been reported to date. The aim of the current proposed study is to compare the efficacy of dual triggering and conventional triggering among the three IVF populations (high, normal and poor responders).

Conditions

IVF Cycle; Ovarian Stimulation; Egg Retrieval; Pregnancy; Miscarriages; Ovarian Hyperstimulation

Keywords

In vitro fertilization; IVF; Assisted Reproductive Technologies; ART; OHSS; Ovarian hyperstimulation; dual triggering; GnRH

Outcome Measures

Primary Outcomes (6)

• Implantation rate

  14 days post IVF procedure

• Human Chorionic Gonadotropin serum levels

  2-4 weeks post IVF procedure

• Ongoing pregnancy rate

  9 months post IVF procedure

• Miscarriage rate

  9 months post procedure

• Ovarian hyperstimulation syndrome

  Mild OHSS: 1. Grade 1: Abdominal distention, Ovaries \<6 cm 2. Grade 2: Abdominal distention and nausea, vomiting and diarrhea, Ovaries \<6 cm Moderate OHSS: a) Grade 3: Grade II criteria and ultrasound ascites/weight gain, Ovaries 6-12 cm Severe OHSS: 1. Grade 4: Ascites/hydrothorax, Ovaries \>12 cm 2. Grade 5: Ascites/hydrothorax and hypovolemia, hemoconcentration, coagulation disorder, oliguria, shock, Ovaries \>12 cm

  7 days post IVF procedure

• Fetal heartbeat measured by ultrasound

  2-4 weeks post IVF procedure

Secondary Outcomes (5)

• Number of retrieved oocytes

  5 days post IVF procedure

• Number of retrieved Meiosis II oocytes

  5 days post IVF procedure

• Fertilization rate

  5 days post IVF procedure

• Number of Day 3 embryos/eggs retrieved

  5 days post IVF procedure

• Number of blastocysts/eggs retrieved

  5 days post IVF procedure

Study Arms (6)

Study group: High Responders

EXPERIMENTAL

1000 units hCG

Drug: Ovulation induction with hCG and Lupron (GnRH agonist)

Control group: High Responders

NO INTERVENTION

1000 units hCG

Study group: Normal Responders

EXPERIMENTAL

5000 units hCG

Drug: Ovulation induction with hCG and Lupron (GnRH agonist)

Control group: Normal Responders

NO INTERVENTION

5000 units hCG

Study group: Low Responders

EXPERIMENTAL

10000 units hCG

Drug: Ovulation induction with hCG and Lupron (GnRH agonist)

Control group: Low Responders

NO INTERVENTION

10000 units hCG

Interventions

Ovulation induction with hCG and Lupron (GnRH agonist) DRUG

Patients treated for infertility are categorized as a low-, normal- or high responder according to their estimated ovarian response to hormonal stimulation. This classification dictates the hormonal stimulation regimen that they will receive. In contrast to hCG triggering, GnRHa triggering is characterized by simultaneous LH and FSH surges, similar to natural ovulation. A combination of GnRHa plus hCG for triggering creates simultaneous LH and FSH surges by the GnRHa, which resembles physiologic ovulation triggering, together with sustained LH-like activity from the hCG, stimulating the corpus luteum to excrete sufficient hormonal endometrial support.

Study group: High Responders; Study group: Low Responders; Study group: Normal Responders

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• AMH \> 29 pmol/L
• AFC \> 16
• Previous OHSS
• Previous cycle cancellation due to OHSS risk
• Previous coasting
• informed consent obtained
• Must be 18 years or older
• Ability to speak and read English, or understand French, Mandarin, Cantonese, Arabic, or Filipino.

You may not qualify if:

• Chronic disease
• Hypogonadotrophic hypogonadism
• Untreated uterine abnormalities
• E2\>4000 pg/ml (\>14,680 pmol/L) on trigger day. These very high risk patients will undergo GnRHa only trigger and will be excluded from the trial.
• B) Dual triggering vs. 5000 units hCG in normal responders
• Age above 18 years and less than 40 years
• Do not fulfill criteria for poor responder or high responder
• Age \> 40 or other risk factor for decreased ovarian reserve (ex. ovarian surgery)
• Single abnormal test for ovarian reserve (AFC \< 6 or AMH \< 8 pmol/L)
• Previous poor response in previous cycle: cancellation or \< 4 retrieved oocytes in response to daily 150 FSH units
• AMH \> 29 pmol/L
• AFC \> 16
• Previous OHSS
• Previous cycle cancellation due to OHSS risk
• Previous coasting

Sponsors & Collaborators

• Create Fertility Center: lead

Study Sites (1)

Create Fertility Centre

Toronto, Ontario, M5G1N8, Canada

RECRUITING

Related Publications (33)

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MeSH Terms

Conditions

Abortion, Spontaneous

Interventions

Ovulation Induction; Leuprolide; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; 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

• Clifford Librach, MD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noga Weizman, MD

CONTACT

416323772; drweizman@createivf.com

Kevin Quach, MSc

CONTACT

4163237727; kev.quach@mail.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2016
• First Posted: March 22, 2016
• Study Start: October 1, 2015
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2021
• Last Updated: July 20, 2020

Record last verified: 2020-07

Locations

CA (1)