Effect of Sirolimus on Oocyte Quality in Women Undergoing IVF

Pilot Study of Sirolimus for Cycle Priming to Improve Oocyte Quality in Women Undergoing IVF

Poor oocyte (egg before maturation) quality remains a major barrier to IVF success, particularly in women with prior cycles demonstrating low oocyte maturity, poor fertilization rates, or suboptimal embryo development. Preclinical and early clinical evidence suggests that the mTOR pathway plays a critical role in oocyte and follicular development, and pharmacologic inhibition with sirolimus (also known as rapamycin), may improve oocyte competence by adjusting granulosa cell function and follicular aging processes.

We propose a multicenter pilot study enrolling participants at the Center for Human Reproduction (CHR) in New York and at the Division of Reproductive Endocrinology and Infertility at the University of Miami Miller School of Medicine. Participants will be aged 20-45 years with a documented history of poor oocyte quality in at least one prior IVF cycle, defined by low oocyte maturity (<50%), low IVM rates (<50%), poor fertilization (<70%), or suboptimal embryo quality (<50% cleavage-stage embryos or no embryos graded B4 or higher), despite normal ovarian response for age and reserve. After enrollment, participants will undergo ovarian priming with Sirolimus 1 mg orally daily in late luteal phase (from cycle-day 19-21 until menstrual period, hence for a total of 7-10 days), immediately preceding ovarian stimulation for embryo banking and later embryo transfer (after at least 12 weeks).

The primary objective is to evaluate the feasibility, safety, and preliminary efficacy of short-term sirolimus treatment for cycle priming prior to IVF, with the goal of improving oocyte quality and developmental competence. The main outcome will be embryo quality compared with historical cycles, although other secondary outcomes derived from egg quality will be assessed.

Study Overview

• Status: Recruiting
• Conditions: Infertility; IVF; Oocytes; Oocyte Competence; Oocyte Retrieval for IVF
• Intervention / Treatment: Drug: Sirolimus (aka rapamycin)

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: David H. Barad, MD, MS; Phone Number: 212-994-4400; Email: dbarad@thechr.com
• Study Contact Backup: Name: Sonia Gayete Lafuente, MD, Ph.D; Email: sgayete@thechr.com

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • The Center for Human Reproduction
      • Contact: Sonia Gayete Lafuente, MD, Ph.D; Email: sgayete@thechr.com
      • Contact: David H. Barad, MD, MS; Phone Number: 2129944400; Email: dbarad@thechr.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Women eligible for participation in this study will be recruited at the Center for Human Reproduction (CHR) in New York at the Division of Reproductive Endocrinology and Infertility at the University of Miami Miller School of Medicine. Participants must be aged 20-45, have a normal ovarian reserve (≥1.1 ng/mL), and a history of poor oocyte quality observed in at least one prior IVF cycle, defined as:

• <50% maturity rate and/or <50% IVM rate and/or <70% fertilization rate

• Poor embryo quality, defined as:

  • Age 20-37 years: >50% day-3 embryos poorer than 7C4
  • Age 38-45 years: >50% day-3 embryos poorer than 6C3

In addition, inclusion criteria are:

• Known or unknown etiology of poor oocyte quality;
• Normal 46XX karyotype;
• Agreement to be monitored and treated as per the study protocol

Exclusion Criteria:

• Diminished ovarian reserve (AMH <1.1 ng/mL)

• Poor response to prior ovarian stimulation, defined as:

  • Age 20-37 years: < 6 oocytes retrieved in the previous cycle;
  • Age 38-45 years: < 4 oocytes retrieved in the previous cycle;

• Severe male factor

• Karyotype abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ovarian priming; This is a prospective, single-arm, stratified pilot study with two prespecified age strata: Age 20-37 -No Qualifying embryos AND Age 38-45 -No Qualifying embryos. A total of 20 participants will be enrolled at the CHR, 10 per age stratum.	Drug: Sirolimus (aka rapamycin); Ovarian priming with Sirolimus 1 mg orally daily in late luteal phase (from cycle-day 19-21 until menstrual period, hence for a total of 7-10 days), immediately preceding ovarian stimulation for embryo banking and later embryo transfer (after at least 12 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder vs. non-responder to rapamycin priming	Binary outcome defined as responder vs. non-responder to rapamycin priming in the post-intervention cycle. A "responder" is defined as achieving at least one Day-3 embryo that meets the prespecified qualifying embryo criteria outlined below.; Age 20-37 years: at least 7C4 (≥7 cells and fragmentation grade ≥4, any cell symmetry grade A/B/C); Age 38-45 years: at least 6C3 (≥6 cells and fragmentation grade ≥3, any cell symmetry grade A/B/C)	Ovarian priming 7-10 days, immediately preceding ovarian stimulation for embryo banking and later embryo transfer (after at least 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of qualifying Day-3 embryos per cycle, distribution of Day-3 cell number and combined morphology grades	• And if available: Day-5 development metrics and clinical outcomes (reported descriptively only)	Ovarian priming 7-10 days, immediately preceding ovarian stimulation for embryo banking and later embryo transfer (after at least 12 weeks)

Collaborators and Investigators

• Sponsor: Center for Human Reproduction
• Collaborators: University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2026
• Primary Completion (Estimated): February 25, 2029
• Study Completion (Estimated): February 25, 2030

Study Registration Dates

• First Submitted: November 9, 2026
• First Submitted That Met QC Criteria: November 9, 2026
• First Posted (Actual): November 13, 2026

Study Record Updates

• Last Update Posted (Actual): November 13, 2026
• Last Update Submitted That Met QC Criteria: November 9, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Organic Chemicals; Macrolides; Lactones; Sirolimus
• Other Study ID Numbers: 0205206-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes