Effectiveness of Low Dose Gonadotropin Stimulation Protocol Vs High Dose Gonadotropin Protocol in Poor Responders

NCT06778733 | Completed Early Phase 1 FDA Drug

• 1 other identifier: ARETAIEION IVF UNIT
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

In the present study we examined the effect of addition of CC to a low dose gonadotropin (150 IU/day) / GnRH antagonist protocol in comparison to a high gonadotropin dose (300 IU/day) regiment (short protocol) in women with poor ovarian responce (POR).

Conditions

Female Infertility

Keywords

Clomiphene Citrate; IVF; Gonadotrophins; pregnancy rates; ovarian reserve; Low-dose gonadotrophins

Outcome Measures

Primary Outcomes (1)

• Ongoing pregnancy rates

  succesfull clinical pregnancy after performing ultrasound on 12 weeks of pregnancy

  28 months from start of study

Secondary Outcomes (6)

• Number of follicles

  24 months from start of study

• Number of mature oocytes

  24 months from start of study

• Fertilization rate

  24 months from start of study

• Total number of embryos in each group

  24 months from start of study

• Biochemical pregnancy rates

  24 months from start of study

Study Arms (2)

Clomiphene Citrate (CC)/r-FSH

ACTIVE COMPARATOR

Administration of 100mg/day Clomiphene citrate (CC) from day 3 to day 7 of the cycle (5 days) in combination with low-dose gonadotropins (150IU) according to a short stimulation GnRh antagonists protocol. Treatment schedule: Serum AMH levels were measured before the stimulation began. Estradiol and FSH levels were measured on the third day of the participants' menstrual cycle. Ovarian stimulation started on the same day with 150 IU of recombinant human Follicle-Stimulating Hormone (r-FSH) after a transvaginal ultrasound was performed, provided that serum FSH levels were below 16 mIU/ml and estradiol levels were under 70 pg/ml (r-FSH group). All patients underwent routine monitoring with transvaginal ultrasound. The GnRH antagonist cetrorelix acetate, at a dose of 0.25 mg/day was given when a dominant follicle reached 14 mm in diameter. Oocyte retrieval (OPU) was performed 34-36 hours after hCG administration followed by IVF/ICSI and embryo transfer on day 3 after OPU

Drug: Clomiphane citrate; Drug: recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)

High-dose Gonadotropins (r-FSH)

ACTIVE COMPARATOR

Patients in this group will be stimulated according to the high-dose short r-FSH antagonist protocol. Treatment schedule: Ovarian stimulation started on day 3 with 300 IU of recombinant human Follicle-Stimulating Hormone (r-FSH) after a transvaginal ultrasound was performed, provided that serum FSH levels were below 16 mIU/ml and estradiol levels were under 70 pg/ml (r-FSH group). All patients underwent routine monitoring with transvaginal ultrasound and serum estradiol measurements. The GnRH antagonist cetrorelix acetate, at a dose of 0.25 mg/day, was given when a dominant follicle reached 14 mm in diameter. Oocyte retrieval (OPU) was performed 34-36 hours after hCG administration, followed by IVF/ICSI and embryo transfer on day 3 after OPU.

Drug: recombinant human Follicle-Stimulating Hormone (r-FSH-alfa)

Interventions

Clomiphane citrate DRUG

Clomiphene citrate 100mg/day from day 3 to day 7 of the cycle (5 days) will be added to the low-dose (150 IU) short GnRh antagonist protocol (recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) (Gonal-f; Merck Serono Hellas AE))

Also known as: Clomiphene citrate 50mg/tab, Serpafar 50mg/tab

Clomiphene Citrate (CC)/r-FSH

recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) DRUG

All patients will undergo ovarian stimulation with the standard-dose GNRH-antagonist protocol. Ovarian stimulation will be initiated with 150 IU of of recombinant human Follicle-Stimulating Hormone (r-FSH-alfa) (Gonal-f; Merck Serono Hellas AE)

Also known as: Gonal-f 150 Iu/day, Gonal-f 300 IU/day

Clomiphene Citrate (CC)/r-FSH; High-dose Gonadotropins (r-FSH)

Eligibility Criteria

• Age: 30 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Advanced maternal age (≥40 years) or any other risk factor for POR
• A previous POR (≤3 oocytes with a conventional stimulation protocol)
• An abnormal ovarian reserve test (Day 3 follicle-stimulating hormone (FSH) \> 12 mIU/ml
• Anti-Müllerian hormone (AMH) \< 2ng/ml).

You may not qualify if:

• The succesful ongoing pregnancy after the first stimulation.

Sponsors & Collaborators

• University of Athens: lead

Study Sites (2)

Aretaieion University Hospital

Athens, Attica, Greece

Location

Aretaieion University Hospital

Athens, Greece

Location

Related Publications (3)

• Pilehvari S, ShahrokhTehraninejad E, Hosseinrashidi B, Keikhah F, Haghollahi F, Aziminekoo E. Comparison Pregnancy Outcomes Between Minimal Stimulation Protocol and Conventional GnRH Antagonist Protocols in Poor Ovarian Responders. J Family Reprod Health. 2016 Mar;10(1):35-42.

  PMID: 27385972 BACKGROUND

• Moffat R, Hansali C, Schoetzau A, Ahler A, Gobrecht U, Beutler S, Raggi A, Sartorius G, De Geyter C. Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders. Hum Reprod. 2021 Mar 18;36(4):987-997. doi: 10.1093/humrep/deaa336.

  PMID: 33367742 BACKGROUND

• Liu S, Liu X, Li H, Liu M, Lv Y, Li Y. Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing in vitro fertilization treatment: a retrospective cohort study. Hum Fertil (Camb). 2023 Dec;26(5):1080-1086. doi: 10.1080/14647273.2022.2109069. Epub 2022 Aug 11.

  PMID: 35950570 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Infertility, Female

Interventions

Clomiphene; follitropin alfa

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Olga Triantafyllidou, MD,

  University of Athens School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Single
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obstetrics and Gynecology, Head of the Department

Model Details: Prospective cohort study

Study Record Dates

• First Submitted: October 5, 2024
• First Posted: January 16, 2025
• Study Start: January 1, 2022
• Primary Completion: January 1, 2024
• Study Completion: April 30, 2024
• Last Updated: January 16, 2025

Record last verified: 2025-01

Locations

GR (2)