InfertilityPhase 3PREGnantNCT04173169
Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis
A Phase 3 study testing Elagolix 200 MG in people with Infertility and Endometriosis, run by Yale University at 5 sites in United States.
Trial summary
A Phase 3 clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility, Endometriosis
- What is being tested?
- Elagolix 200 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 5 sitesUnited States
- Study dates
- 15 Mar 2022to 2 May 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women who plan to undergo IVF for treatment of infertility.
- Age ≥18 and <40 years at time of egg retrieval or signing informed consent.
- Documentation of diagnosis of endometriosis by surgical visualization of endometriosis (laparoscopy or laparotomy) or diagnosis by pathology within the last 10 years before the initial trial entry visit or documentation of ovarian endometrioma >2 cm or two or more smaller endometriomas that total >2 cm in diameter. If entry is based on the presence of an endometrioma, transvaginal ultrasound evaluation must document the same unambiguous endometrioma on two separate occasions in more than one menstrual cycle. Images will be printed or transmitted electronically and read centrally by investigators at Yale to assure uniform diagnostic criteria (classic ground glass appearance) are applied.
- Body mass index (BMI) of 18-40 kg/m2 (both inclusive) at screening.
- AMH > 0.5ng/ml, within 12 months of a fresh IVF cycle start. For frozen embryo transfers (FET) , AMH level eligibility criteria may not be met as long as the patient has at least one good quality blastocyst stored for the FET.
- No known uterine cavity abnormalities at time of screening. Uterine cavity assessment by sonohysterogram or hysteroscopy within 12 months of embryo transfer indicating absence of focal intracavitary pathology and hence establishing adequate cavity at the time of embryo transfer. Ultrasound or MRI features suggestive of adenomyosis will be acceptable for inclusion. Type 3 fibroids are allowed up to 4cm size.
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- Presence of at least one ovary with no clinically significant abnormalities other than endometrioma. For eligible women with evidence of a hemorrhagic ovarian cyst, a repeat US will be needed in a subsequent menstrual cycle to ensure persistent cyst for patient to be deemed eligible.
- Negative urine or cervical swab for gonorrhea and chlamydia within 12 months of screening.
- Willing and able to comply with trial procedures, including reporting of obstetrical outcomes after delivery.
Who cannot join
- Use of depot GnRH agonists within 6 months of study start. Use of subcutaneous antagonists or nasal agonist within 2 months of study start unless part of regular IVF or previous IUI cycle°.
- Use of depot medroxyprogesterone acetate (MPA) (injectable) or birth control implants (e.g., Implanon® or Nexplanon®) within 6 months of study start°.
- Continuous use of oral progestins (MPA, NETA) within 1 month of study start°.
- Use of aromatase inhibitors, danazol or hormonal contraceptives (Including combined oral contraceptive pill, progestin-only pill, transdermal patch or contraceptive ring, or double barrier contraception) within 1 month of study start.
- Pregnancy greater than 8 weeks in length within the last 6 months.
- Number of previous IVF/ICSI attempts ≥3 unsuccessful (negative pregnancy test).
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- Presence of hydrosalpinx measuring >2cm on ultrasound, untreated endometrial polyps or intrauterine adhesions.
- Abnormal cytology on a cervical screening based on the American College of Obstetricians and Gynecologists (ACOG) guidelines and patient age. (CIN1 or HPV allowed to participate in the study, CIN2 excluded unless treated and cleared, CIN3 excluded).
- History of malignancy within 5 years of the start of screening, except for treated basal cell carcinoma and squamous cell carcinoma of the skin.
- Any thoughts of suicide in the last 12 months per self-report, or documented in the electronic medical record (EMR).
- Hypersensitivity to the study drugs.
- Planned surgical treatment of endometriosis or planned surgery in the abdominal-pelvic area within the duration of the trial.
- Untreated abnormal prolactin or TSH
- Any conditions that preclude pregnancy.
- Patients with a known history of a low-trauma fracture or other risk factors for osteoporosis or bone loss.
- Patients with cirrhosis or abnormal LFTs per self report or documented in the electronic medical record (EMR).
- Exclusion criteria number 1,2, and 3 are not required to be met by individuals in the standard of care arm of the study. The study team will collect the information regarding whether the subject has used these drugs in the aforementioned time frame using the concomitant medication log and the individual will be allowed to participate in the study under the standard of care arm only.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Colorado Department of Obstetrics & Gynecology
Aurora, Colorado, 80045
Johns Hopkins, Division of Reproductive Science and Women's Health Research
Baltimore, Maryland, 21205
Northwestern University Department of Obstetrics and Gynecology
Chicago, Illinois, 60611
Duke Fertility
Morrisville, North Carolina, 27560
Yale School of Medicine Dept.of Ob/Gyn & Reproductive Sciences
New Haven, Connecticut, 06520
About this study
Official title: Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis - A Prospective Clinical Trial
A Phase 3 clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to those not pretreated with GnRH antagonist.
Read the detailed description
Infertility is a common complication of endometriosis; while IVF successfully treats endometriosis-associated infertility, pregnancy rates are diminished compared to other etiologies of infertility. The study's long- term objectives are to better identify and treat endometriosis related infertility. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to those not pretreated with GnRH antagonist. The use of gonadotropin releasing hormone (GnRH) agonist prior to IVF has been suggested to improve success, however studies have been small and rarely reported live birth rates. Further, use of this approach is limited by the long treatment time required. Recent approval of an oral GnRH antagonist for endometriosis provides a novel option for women with endometriosis who are undergoing IVF. This agent avoids parenteral administration and the prolonged delay in initiation of action as was seen with GnRH agonists. There have been no studies on the efficacy of GnRH antagonists for the treatment of endometriosis-related infertility. The investigators propose a clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. Participants will include those who agree to be randomized and those who do not want to be randomized. Those who agree to be randomized will be randomly assigned to either the elagolix group or placebo group. Those who do not want to be randomized can choose either the active treatment elagolix and follow the same procedures as those agreeing to be randomized or continue their ongoing or planned IVF and follow standard of care (SOC) (SOC IVF) if they do not want to delay the IVF procedure.
- Conditions
- Infertility, Endometriosis
- Being tested
- Elagolix 200 MG, Placebo or SOC IVF
- Medical subject headings
- Infertility, Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elagolix 200 MGDrug
Also called Orlissa
Elagolix tablet
Placebo or SOC IVFOther
Sugar pill manufactured to mimic Elagolix 200mg
| Study group | Role | What they receive |
|---|---|---|
| Pre-IVF Treatment with 60 day course of oral GnRH antagonist | Active comparator | For those who agree to be randomized, subjects will be randomized to elagolix 200mg BID. The medication will be taken orally and subjects will be counseled to take the medication at the same time each day. This arm will also include participants who do not want to be randomized while choose elagolix. Receives: Drug: Elagolix 200 MG |
| Pre-IVF Treatment with 60 day course of Placebo or SOC IVF | Other | For those who agree to be randomized, subjects will be randomized to placebo, BID. The medication will be taken orally and subjects will be counseled to take the medication at the same time each day. This arm will also include participants who want to continue their ongoing or planned IVF and follow standard of care (SOC) (SOC IVF) if they do not want to delay the IVF procedure. Receives: Other: Placebo or SOC IVF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live Birth Rate
The percentage of the number of participants with a live birth at ≥24 weeks of gestation out of those who were enrolled in the study
Measured: Up to 15 months
Secondary outcomes (9)
Fertilization Rate
The percentage of the total number of fertilized oocytes (two pronuclei) out of the total number of injected/inseminated oocytes across all participants in each Arm/Group who had the current or previous IVF data
Measured: Up to 9 months
Number of Embryos Transferred
Number of embryos transferred per participant
Measured: Up to 9 months
Implantation Rate
The percentage of the total number of gestation sacs visible by Ultrasound out of the total number of transferred embryos across all participants in each Arm/Group who completed embryo transfer
Measured: Up to 9 months
Biochemical Pregnancy Rate
The percentage of the number of participants with positive pregnancy tests following embryo transfer out of those who were enrolled in the study
Measured: Up to 9 months
Clinical Pregnancy Rate
The percentage of the number of participants with ultrasound evidence of intrauterine gestational sac with fetal cardiac activity out of those who were enrolled in the study
Measured: Up to 10 months
Miscarriage Rate
Percentage of the number of participants with a pregnancy loss out of those who have achieved pregnancy
Measured: Up to 10 months
Overall Pregnancy Complication Rate
Percentage of the number of participants who had the overall pregnancy complication out of those who have achieved pregnancy. Overall pregnancy complication including any of the following: preterm delivery, preeclampsia, gestational diabetes, intrauterine growth restriction, incompetent cervix, premature rupture of membrane, incidence of abnormal placentation (placenta previa, accreta, increta, percreta, abruption), bleeding in pregnancy (antepartum or postpartum)
Measured: Up to 15 months
Gestation Age at Delivery
Gestation age (weeks) at delivery per infant delivered
Measured: Up to 15 months
Infant Birth Weight
Infant birth weight (gram) per infant delivered.
Measured: Up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2019
- Study start15 Mar 2022
- Primary completion2 May 2025
- Study completion2 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Half of the subjects (200, randomized or not randomized) will receive elagolix 200mg twice a day (BID) and the other half of subjects will receive placebo BID or SOC IVF (200, placebo or SOC IVF). Elagolix or placebo will be taken for a minimum of 60 days before IVF cycle start. For convenience of IVF cycle scheduling, participants may receive up to an additional 14 days of intervention (elagolix or placebo) beyond the minimum 60 days of pre-IVF treatment, such that the last dose of study intervention (elagolix or placebo) is received no more than 24 hours before start of IVF treatment protocol.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Colorado, Denver, Northwestern University, University of North Carolina
- Responsible party
- Sponsor
- Investigators
- David Weinberg, PhD, Study director, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Hugh Taylor, MD, Principal investigator, Yale UniversityHeping Zhang, PhD, Study director, Yale UniversityNanette Santoro, MD, Study director, University of Colorado, DenverEmily Jungheim, MD, Study director, Northwestern UniversitySteven Young, MD, PhD, Study director, Duke UniversityAbisola Tepede, PharmD, Study director, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04173169
- Sponsor's protocol ID
- 2000027121
- Other IDs
- 1R01HD100336-01
- Acronym
- PREGnant
- Status last verified
- May 2026
- First submitted
- 20 Nov 2019
- Last updated
- 12 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We have a plan to submit data and samples collected by the trial to NICHD DASH. The informed consent will include permission to bank these samples. The processes included initial data and documentation preparation (e.g., codebooks, protocols, informed consent for data sharing), data quality control, and submission.
Publications
Taylor H, Li HJ, Carson S, Flores V, Pal L, Robbins J, Santoro NF, Segars JH, Seifer D, Huang H, Young S, Zhang H. Pre-IVF treatment with a GnRH antagonist in women with endometriosis (PREGNANT): study protocol for a prospective, double-blind, placebo-controlled trial. BMJ Open. 2022 Jun 17;12(6):e052043. doi: 10.1136/bmjopen-2021-052043.
PubMed 35715184Pretzel S, Kuhn K, Pal L, Polotsky A, Taylor HS, Zhang H, Robins J, Young SL, Santoro N. Willingness of Women with Endometriosis Planning to Undergo IVF to Participate in a Randomized Clinical Trial and the Effects of the COVID-19 Pandemic on Potential Participation. Reprod Sci. 2022 Feb;29(2):620-626. doi: 10.1007/s43032-021-00705-0. Epub 2021 Aug 6.
PubMed 34363198