Effect of Semaglutide on Embryo Quality in Overweight and Obese Patients Undergoing In Vitro Fertilization.

Official title

Effect of Semaglutide on Embryo Quality in Overweight and Obese Patients Undergoing In Vitro Fertilization. A Randomized Controlled Trial

Overview

This is a randomized, controlled clinical trial with a two-sided superiority hypothesis. The study evaluates whether a 12-week pre-treatment with semaglutide prior to ovarian stimulation improves the number of good-quality blastocysts in overweight and obese women undergoing in vitro fertilization (IVF), compared to no pre-treatment.

Detailed description

Overweight and obese women (BMI 27-40 kg/m²) aged ≤38 years with adequate ovarian reserve (AMH ≥1 ng/mL or AFC ≥6) will be enrolled. Participants will be randomized in a 1:1 ratio to receive either 12 weeks of semaglutide pre-treatment (intervention group) or no pre-treatment (control group) before undergoing standard ovarian stimulation.

Embryos will be cultured to the blastocyst stage and cryopreserved (freeze-all strategy). In the semaglutide group, embryo transfer will occur after an 8-week washout from the last semaglutide dose.

Primary outcome: number of good-quality blastocysts on day 5. Secondary outcomes: embryo morphokinetics, fertilization rate, number of MII oocytes, number of COCs, total blastocyst formation rate, number of cryopreserved embryos, and pre/post semaglutide changes in weight, BMI, waist circumference, AMH, and AFC.

The study has been designed with a superiority hypothesis to detect a difference of 1.5 good-quality blastocysts between groups, with 80% power and a two-sided alpha of 0.05.

Interventions

• Drug Semaglutide
  Participants in this group will receive semaglutide for 12 weeks before ovarian stimulation (0.25 mg/week in weeks 1-4, 0.5 mg/week in weeks 5-8, and 1 mg/week in weeks 9-12). After pre-treatment, controlled ovarian stimulation will be initiated with 225-300 IU/day of rFSH, GnRH antagonist (0.25 mg/day) starting when follicles reach ≥14 mm, and ovulation triggered with triptorelin 0.2 mg when 2-3 follicles reach ≥18 mm. Oocyte retrieval will occur 34-36 hours later, followed by IVF/ICSI. Embryos
• Other No pre-treatment
  Participants in this group will undergo standard ovarian stimulation without semaglutide pre-treatment. Stimulation will begin with 225-300 IU/day of rFSH, GnRH antagonist (0.25 mg/day) starting when follicles reach ≥14 mm, and ovulation triggered with triptorelin 0.2 mg when 2-3 follicles reach ≥18 mm. Oocyte retrieval will be performed 34-36 hours later, followed by IVF/ICSI. Embryos will be cultured to the blastocyst stage and cryopreserved. Embryo transfer will follow standard clinical pract

Primary outcome measures

• Number of good quality blastocysts (GQB) [Time frame: Assessed once per participant, from oocyte retrieval (Day 0) to Day 5 of embryo culture, when embryos reach blastocyst stage.]

Secondary outcome measures (12)

• Days of stimulation [Time frame: From stimulation start (Stimulation Day 1) to trigger day, approx. 8-12 days per participant.]
• Total dose of Gonadotropins [Time frame: From first day of ovarian stimulation to trigger day (8-12 days total).]
• Number COCs [Time frame: Assessed on day of oocyte retrieval, approx. 34-36 hours after ovulation trigger.]
• Number MII [Time frame: Assessed on same day as oocyte retrieval, after denudation and classification]
• Fertilization rate [Time frame: Assessed on Day 1 after ICSI, 16-18 hours post-injection]
• Time of appearance of the 2nd polar body (tPB2) [Time frame: Recorded via time-lapse system, within first 8 hours post-ICSI (Day 0).]
• Time of pronuclei appearance (tPNa) [Time frame: Measured on Day 1 post-ICSI using time-lapse monitoring.]
• Evaluation of both pronuclei (PN) [Time frame: Assessed during pronuclear stage on Day 1 post-ICSI.]
• Time of pronuclei disappearance (tPNf) [Time frame: Recorded by time-lapse imaging, approx. 20-24 hours post-ICSI.]
• Time of division from 2 to 8 cells [Time frame: Tracked continuously via time-lapse, from Day 2 to Day 3 post-ICSI]
• Time of compaction (tSC) [Time frame: Tracked by time-lapse imaging on Day 4 post-ICSI]
• Time of morula (tM) [Time frame: Recorded by time-lapse on Day 4 post-ICSI.]

Eligibility criteria

Inclusion criteria

• ≤ 38 years
• AMH >= 1 ng/mL or AFC >= 6
• Body mass index (BMI) between 27 kg/m2 and 40 kg/m2
• Scheduled for IVF with freeze-all strategy

Exclusion criteria

• Severe male factor (sperm concentration <5M/mL)
• Type 2 diabetes mellitus
• Prior use of GLP-1 Ras within the past year
• Uncontrolled thyroid disorders
• Contraindications to IVF or semaglutide treatment
• Patients with chronic inflammatory diseases
• Family history of hereditary or chromosomal diseases
• Use of glucocorticoids or immunosuppressants
• PGT-A
• Use of medications affecting metabolism or inflammation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 5 centers

• Dexeus Mujer Sabadell — Sabadell
• Dexeus Mujer Sant Cugat — Sant Cugat del Vallès
• Dexeus Mujer Reus — Reus
• Departamento de Ginecología Obstetricia y Reproducción. Hospital Universitari Dexeus — Barcelona
• Dexeus Mujer Tarragona — Tarragona

Publications

• Amiri M, Ramezani Tehrani F. Potential Adverse Effects of Female and Male Obesity on Fertility: A Narrative Review. Int J Endocrinol Metab. 2020 Sep 28;18(3):e101776. doi: 10.5812/ijem.101776. eCollection 2020 Jul. PMID 33257906
• Bader S, Bhatti R, Mussa B, Abusanana S. A systematic review of GLP-1 on anthropometrics, metabolic and endocrine parameters in patients with PCOS. Womens Health (Lond). 2024 Jan-Dec;20:17455057241234530. doi: 10.1177/17455057241234530. PMID 38444070
• Dag ZO, Dilbaz B. Impact of obesity on infertility in women. J Turk Ger Gynecol Assoc. 2015 Jun 1;16(2):111-7. doi: 10.5152/jtgga.2015.15232. eCollection 2015. PMID 26097395
• Gautam D, Purandare N, Maxwell CV, Rosser ML, O'Brien P, Mocanu E, McKeown C, Malhotra J, McAuliffe FM; FIGO Committee on Impact of Pregnancy on Long-term Health and the FIGO Committee on Reproductive Medicine, Endocrinology and Infertility. The challenges of obesity for fertility: A FIGO literature review. Int J Gynaecol Obstet. 2023 Jan;160 Suppl 1(Suppl 1):50-55. doi: 10.1002/ijgo.14538. PMID 36635080
• Goldberg AS, Boots CE. Treating obesity and fertility in the era of glucagon-like peptide 1 receptor agonists. Fertil Steril. 2024 Aug;122(2):211-218. doi: 10.1016/j.fertnstert.2024.05.154. Epub 2024 May 27. PMID 38810863
• He Y, Lu Y, Zhu Q, Wang Y, Lindheim SR, Qi J, Li X, Ding Y, Shi Y, Wei D, Chen ZJ, Sun Y. Influence of metabolic syndrome on female fertility and in vitro fertilization outcomes in PCOS women. Am J Obstet Gynecol. 2019 Aug;221(2):138.e1-138.e12. doi: 10.1016/j.ajog.2019.03.011. Epub 2019 Mar 22. PMID 30910544
• Jensterle M, Janez A, Fliers E, DeVries JH, Vrtacnik-Bokal E, Siegelaar SE. The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Hum Reprod Update. 2019 Jul 1;25(4):504-517. doi: 10.1093/humupd/dmz019. PMID 31260047
• Khan D, Ojo OO, Woodward OR, Lewis JE, Sridhar A, Gribble FM, Reimann F, Flatt PR, Moffett RC. Evidence for Involvement of GIP and GLP-1 Receptors and the Gut-Gonadal Axis in Regulating Female Reproductive Function in Mice. Biomolecules. 2022 Nov 23;12(12):1736. doi: 10.3390/biom12121736. PMID 36551163

Identifiers

NCT: NCT07242534 · FSD-SEM-2025-14 · 2025-522525-34-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗