Clinical trial NCT06778733: Effectiveness of Low Dose Gonadotropin Stimulation Protocol Vs High Dose Gonadotropin Protocol in Poor Responders
Official title: The Effect of Clomiphene Citrate Administration in Combination with Low Dose (150 IU) of Gonadotropins Vs High Dose Gonadotropin Protocol in Poor Responders. Impact on Stimulation Characteristics and Pregnancy Outcome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Female Infertility
Keywords: Clomiphene Citrate
IVF
Gonadotrophins
pregnancy rates
ovarian reserve
Low-dose gonadotrophins
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2025-01-16
Enrollment: 22
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective cohort study
Primary purpose: TREATMENT

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).

Detailed description: 22 patients diagnosed with poor ovarian response, aged 35-43 years, were enrolled in the study. The definition of poor response was based on the presence of at least one of the following criteria: Age equal or over 40 years old or other cause of subfertility, AFC less than 5-7, AMH 0.5-1,1ng/ml , a previous POR (≤3 oocytes with a conventional stimulation protocol or cancellation due to poor response) . All patients received appropriate counselling . Early follicular phase FSH and estradiol (E2) were measured prior to the initiation of treatment. All women had measurements of serum FSH and estradiol and a pelvic sonogram on the second day of their cycle. Providing that serum FSH level was less than 16 mIU/ml and estradiol level less than 70 pg/ml on cycle day2 , ovarian stimulation was initiated with 300 IU of gonadotropins either in the form of a combination of highly purified urinary FSH and LH or with a combination of recombinant FSH and recombinant LH. All patients were re-evaluated on day 5 of the stimulation, and dosage adjustments were made and the antagonists (Cetrorelix or ganirelix 0.25 mg/day) were initiated when at least one follicle reached a diameter of 14mm . When at least 2 follicles reached an average diameter of 18 mm, final oocyte maturation was triggered with 10,000IU of hCG ( Ovitrelle, Greece Inc.). Oocyte retrieval was performed 34 to 36 hours later. All patients underwent ICSI. Patients with successful fertilization underwent embryo transfer under sonographic guidance on day 5 after retrieval. Serum β-hCG levels were measured 12 days after oocyte retrieval, and clinical pregnancy was confirmed by transvaginal ultrasound 14 days later. Ongoing pregnancy was confirmed at 12 weeks by ultrasound. In case of negative pregnancy test result the same participants received CC (100 mg/day) from day 3 to day 7 of the menstrual cycle, in combination with low-dose gonadotropins (150 IU/day) until the day of hCG administration. The primary outcome measure was ongoing pregnancy rates. Secondary outcomes included the number of follicles, the number of mature oocytes, fertilization rate, total number of embryos and embryo quality in each group. Furthermore, we included biochemical pregnancy rates and miscarriage as secondary outcomes as well.

Eligibility criteria: The inclusion criteria, established by the European Society of Human Reproduction and Embryology (ESHRE), define POR as the presence of at least two of the following features, had to be met:

* 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).

Exclusion Criteria:

The succesful ongoing pregnancy after the first stimulation.

Primary outcomes:
measure: Ongoing pregnancy rates
timeFrame: 28 months from start of study
Secondary outcomes:
measure: Number of follicles
timeFrame: 24 months from start of study
measure: Number of mature oocytes
timeFrame: 24 months from start of study
measure: Fertilization rate
timeFrame: 24 months from start of study
measure: Total number of embryos in each group
timeFrame: 24 months from start of study
measure: Biochemical pregnancy rates
timeFrame: 24 months from start of study
measure: Miscarriage rates
timeFrame: 28 months from start of study
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Aretaieion University Hospital
state: Attica
city: Athens
country: Greece
facility: Aretaieion University Hospital
Study officials:
affiliation: University of Athens School of Medicine
name: Olga Triantafyllidou, MD,
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.