Dehydroepiandrosterone Versus Growth Hormone in Women Undergoing ICSI With Expected Poor Ovarian Response

Subfertility Clinical Trial

Official title:

Dehydroepiandrosterone Versus Growth Hormone in Women Undergoing ICSI With Expected Poor Ovarian Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02736591
• Other study ID #: sub 13
• Status: Recruiting
• Phase: Phase 3
• First received: April 8, 2016
• Last updated: July 3, 2016
• Start date: June 2016

Study information

• Verified date: July 2016
• Source: Cairo University
• Contact: AbdelGany M Hassan, MRCOG, MD
• Phone: +201017801604
• Email: abdelgany2[@]gmail.com
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Higher Education
• Study type: Interventional

Clinical Trial Summary

300 women with expected poor ovarian response (POR) undergoing in vitro fertilization or intra-cytoplasmic sperm injection (ICSI) will be randomly divided into 2 equal groups using computer generated random numbers. Group 1 will receive Dehydroepiandrosterone (DHEA) 25 mg ( DHEA 25mg, Natrol , USA) t.d.s daily for 12 weeks before starting IVF/ICSI cycle and a placebo similar to growth hormone (GH) daily from day 6 of stimulation until the day of human chorionic gonadotrophin (hCG) trigger. Group 2 will receive an oral placebo t.d.s. daily for 12 weeks before ICSI in addition to GH (Somatotropin, Sedico, Egypt) 4 IU on day 6 of hMG stimulation in a daily dose of 2.5 mg subcutaneous (SC) until the day of hCG triggering.

Patients included in the study will be subjected to full history taking and clinical examination. On the second day of menstruation serum FSH, LH, Prolactin and Oestradiol will be assessed and the antral follicular count (AFC) will be assessed using a vaginal ultrasound scan. AFC will be defined as the number of follicles measuring 3-10mm.

All patients will have gonadotropin antagonist protocol with Human menopausal gonadotrophin (hMG) stimulation until the day of hCG administration. On the day of hCG administration, ovarian ultrasound scan will be performed using a transvaginal probe. Oocytes will be aspirated 34-36 hours after HCG administration. Oocytes will be fertilized and embryos will be transferred. Both groups will be compared regarding the proportion of ongoing pregnancy.

Description:

The study will be conducted in Cairo university hospitals and Dar Al-Teb Infertility and Assisted conception center, Giza Egypt. All patients attending the centre will be evaluated for expected ovarian response. Patients fulfilling the Bologna criteria definition of poor ovarian response will be invited to participate in the study and to sign informed consent forms.

300 women with expected poor ovarian response undergoing IVF/ICSI will be randomly divided into 2 equal groups using computer generated random numbers. Group 1 will receive DHEA 25 mg ( DHEA 25mg, Natrol , USA) t.d.s daily for 12 weeks before starting IVF/ICSI cycle and a placebo similar to GH daily from day 6 of stimulation until the day of hCG trigger. Group 2 will receive an oral placebo t.d.s. daily for 12 weeks before ICSI in addition to GH Growth hormone (Somatotropin, Sedico, Egypt) 4 IU on day 6 of hMG stimulation in a daily dose of 2.5 mg SC until the day of hCG triggering.

Patients included in the study will be subjected to full history taking and clinical examination. On the second day of menstruation serum FSH, LH, Prolactin and Oestradiol will be assessed and the antral follicular count (AFC) will be assessed using a vaginal ultrasound scan. AFC will be defined as the number of follicles measuring 3-10mm.

All patients will have gonadotropin antagonist protocol with Human menopausal gonadotrophin (HMG) stimulation until the day of (Human chorionic gonadotrophin (HCG) administration. On the second day of menstruation serum FSH, LH, Prolactin and Oestradiol will be assessed and the antral follicular count (AFC) will be assessed using a vaginal ultrasound scan. AFC will be defined as the number of follicles measuring 3-10mm.

The stimulation protocol will start on day 2 using 450-300 IU HMG ( Merional® IBSA, Lugano, Switzerland) and gonadotrophin releasing hormone antagonist, cetrorelix (Cetrotide® Merck Serono, Darmstadt, Germany) 0.025 mg daily. Gonadotropins will be administered for 4 to 5 days, after which the dose will be adjusted according to the ovarian response. The ovarian response will be monitored by transvaginal ultrasound and serum E2 levels. When three or more follicles reached a maximum diameter of 16 mm, highly purified HCG 5000 or 10,000 IU (Choriomon ®IBSA) will be administered. The procedure will be cancelled if less than 3 follicles 16 mm in size are present 12 days after starting gonadotropins despite doses reaching 450 IU. The cycle will be also cancelled if there is risk of ovarian hyperstimulation like massive ovarian enlargement or serum estradiol exceeds 3000pg/L Transvaginal oocyte retrieval will be performed 34-36 h after the administration of HCG. Oocytes will be fertilized either via IVF or ICSI based on the couple's history. Fertilization will be assessed 16-18 h after IVF or ICSI . Embryos will be transferred on Day 3 or 5. Vaginal tablets containing progesterone (Prontogest® IBSA) 400 mg/day will be given when fertilization is confirmed. A pregnancy test will be done 2 weeks after embryo transfer. For patients with a positive pregnancy test, progesterone is to be continued for an additional 4 weeks. Clinical pregnancy will be defined as Visualization of an intrauterine gestational sac 5 weeks after embryo transfer. And ongoing pregnancy will be defined as the sonographic confirmation of fetal heart pulsations at 12 weeks.

Sample size calculation:

Investigators are planning a study of independent cases and controls with 1 control(s) per case. Kotb et al found that the ongoing pregnancy rate in women undergoing IVF/ICSI with expected POR according to the Bologna controls is 0.285. On the other hand Bassiouny et al found that the ongoing pregnancy rate in women undergoing ICSI with expected POR who received growth hormone is 0.147, investigators will need to study 138 case patients who will receive DHEA and 138 patients who will receive GH to be able to reject the null hypothesis that the ongoing pregnancy rates for DHEA and GH are equal with probability (power) 0.8. Investigators will add 12 patients to each arm to account for missing data and dropout patients. The Type I error probability associated with this test of this null hypothesis is 0.05. Investigators will use an uncorrected chi-squared statistic to evaluate this null hypothesis.

The primary outcome will be the ongoing pregnancy rate defined as sonographic confirmation of fetal heart beat at 12 weeks of gestation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 43 Years

Eligibility

Inclusion Criteria:

• women undergoing IVF/ICSI with POR according to the Bologna criteria

Exclusion Criteria:

• Body mass index >35 Kg/m2.

• women with a single ovary.

• Allergy to DHEA.

• Diabetic women on insulin as insulin lowers DHEA levels and might reduce its effectiveness

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Subfertility

Intervention

Drug:
• DHEA
Women will receive oral DHEA 25 mg t.d.s. 12 weeks before ICSI.
• Growth Hormone-Releasing Hormone
Women will receive 4 IU of growth hormone on day 6 of hMG stimulation in a daily dose of 2.5 mg SC until the day of hCG triggering
• Placebo 1
Women will receive an oral placebo similar to DHEA for 12 weeks before ICSI.
• Placebo 2
Women will receive a placebo injection similar to growth hormone daily from day 6 of hMG stimulation until the day of hCG triggering.

Locations

Country	Name	City	State
Egypt	Cairo University Hospitals	Cairo
Egypt	Dar AlTeb subfertility centre	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

Bassiouny YA, Dakhly DM, Bayoumi YA, Hashish NM. Does the addition of growth hormone to the in vitro fertilization/intracytoplasmic sperm injection antagonist protocol improve outcomes in poor responders? A randomized, controlled trial. Fertil Steril. 2016 Mar;105(3):697-702. doi: 10.1016/j.fertnstert.2015.11.026. Epub 2015 Dec 13. — View Citation

Bayoumi YA, Dakhly DM, Bassiouny YA, Hashish NM. Addition of growth hormone to the microflare stimulation protocol among women with poor ovarian response. Int J Gynaecol Obstet. 2015 Dec;131(3):305-8. doi: 10.1016/j.ijgo.2015.05.034. Epub 2015 Aug 23. — View Citation

Dakhly DM, Bayoumi YA, Gad Allah SH. Which is the best IVF/ICSI protocol to be used in poor responders receiving growth hormone as an adjuvant treatment? A prospective randomized trial. Gynecol Endocrinol. 2016;32(2):116-9. doi: 10.3109/09513590.2015.1092136. Epub 2015 Sep 29. — View Citation

Kotb MM, Hassan AM, AwadAllah AM. Does dehydroepiandrosterone improve pregnancy rate in women undergoing IVF/ICSI with expected poor ovarian response according to the Bologna criteria? A randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2016 May;200:11-5. doi: 10.1016/j.ejogrb.2016.02.009. Epub 2016 Feb 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy	ongoing pregnancy will be confirmed by the presence of fetal cardiac pulsations by a transvaginal ultrasound 12 weeks after embryo transfer.	12 weeks after embryo transfer	No
Secondary	Clinical pregnancy	clinical pregnancy will be confirmed by the presence of an intrauterine gestational sac using a transvaginal ultrasound 5 weeks after embryo transfer.	5 weeks after embryo transfer	No