Infertility, Obesity
Conditions
Keywords
Obesity, Overweight, GLP-1 receptor agonist, IVF, ART
Brief summary
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
DRUGSemaglutide
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 will be cultured to blastocyst stage and cryopreserved. Embryo transfer will occur after an 8-week washout from semaglutide.
OTHERNo 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 practice.
Sponsors
Fundacion Dexeus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of good quality blastocysts (GQB) | Assessed once per participant, from oocyte retrieval (Day 0) to Day 5 of embryo culture, when embryos reach blastocyst stage. | (ASEBIR criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of compaction (tSC) | Tracked by time-lapse imaging on Day 4 post-ICSI | — |
| Time of morula (tM) | Recorded by time-lapse on Day 4 post-ICSI. | — |
| Time of cavitation (tSB) | Recorded by time-lapse on Day 5 post-ICSI. | — |
| Time of full blastulation (tB) | Measured by time-lapse on Day 5 of embryo culture | — |
| Total number of day 5 blastocysts | Counted on Day 5 of embryo culture after ICSI | — |
| Blastocyst formation rate, | Calculated on Day 5 based on 2PN embryos reaching blastocyst stage. | the proportion of 2PN zygotes that reach the blastocyst stage |
| Number of embryos cryopreserved | Recorded at time of freezing on Day 5-7 of embryo culture | — |
| Embryo stage (D5, D6, D7) | Assessed at time of embryo cryopreservation on Day 5 to 7 | — |
| Change in AFC | Compared between baseline (Visit 2) and end of semaglutide treatment (Visit 5, Week 12). | before and after the treatment with semaglutide |
| Number MII | Assessed on same day as oocyte retrieval, after denudation and classification | — |
| Fertilization rate | Assessed on Day 1 after ICSI, 16-18 hours post-injection | — |
| Time of appearance of the 2nd polar body (tPB2) | Recorded via time-lapse system, within first 8 hours post-ICSI (Day 0). | — |
| Time of pronuclei appearance (tPNa) | Measured on Day 1 post-ICSI using time-lapse monitoring. | — |
| Evaluation of both pronuclei (PN) | Assessed during pronuclear stage on Day 1 post-ICSI. | — |
| Time of pronuclei disappearance (tPNf) | Recorded by time-lapse imaging, approx. 20-24 hours post-ICSI. | — |
| Days of stimulation | From stimulation start (Stimulation Day 1) to trigger day, approx. 8-12 days per participant. | — |
| Total dose of Gonadotropins | From first day of ovarian stimulation to trigger day (8-12 days total). | — |
| Number COCs | Assessed on day of oocyte retrieval, approx. 34-36 hours after ovulation trigger. | — |
| Change in AMH | Compared between baseline (Visit 2) and end of semaglutide treatment (Visit 5, Week 12). | before and after the treatment with semaglutide |
| Change in BMI | : Measured at baseline, Weeks 4, 8, and 12 of semaglutide treatment (Visits 2-5). | before and after the treatment with semaglutide |
| Time of division from 2 to 8 cells | Tracked continuously via time-lapse, from Day 2 to Day 3 post-ICSI | — |
| Change in WC | : Measured at baseline, Weeks 4, 8, and 12 of semaglutide treatment (Visits 2-5). | before and after the treatment with semaglutide |
Countries
Spain
Contacts
CONTACTNikolaos P Polyzos, MD, PhD
CONTACTIgnacio Rodríguez, MSc
PRINCIPAL_INVESTIGATORNikolaos P Polyzos, MD, PhD
Dexeus Fertility
Outcome results
None listed