POR: Comparison of Ovarian Mild Stimulation and Controlled Ovarian Stimulation in Poor Ovarian Responders

Sponsor

Huang Rui (Other)

Overall Status

Unknown status

CT.gov ID

NCT01926210

Collaborator

(none)

500

Enrollment

Location

Arms

Duration (Months)

13.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, randomized clinical trial to compare the efficiency and safety of mild stimulation and controlled ovarian stimulation protocol on the treatment of POR. The randomization is achieved on the basis of a computer-generated randomization list in a 1:1 ratio.

Condition or Disease	Intervention/Treatment	Phase
Infertility	Other: mild stimulation protocol Other: controlled ovarian stimulation	Phase 4

Detailed Description

500 poor ovarian responders will be equally randomized to two different ovarian stimulation protocol arms,i.e, mild ovarian stimulation(experimental arm) or controlled ovarian stimulation(control arm). In experimental arm, patients will received letrozole 5mg per day from cycle day 3 to 7 and recombinant follicle-stimulating hormone (FSH) 150 international unit (IU) on day 4 and 6. The dose of recombinant FSH is adjusted according to the ovarian response and the gonadotropin-releasing hormone(GnRH)antagonist(Cetrotide) 0.25mg per day is administrated when the estradiol level reaches 200 pg/ml and the serum luteinizing hormone （LH）level rises above 2 times of basal LH level. In control arm,patients will be stimulated with short-acting GnRH agonist long protocol. After complete downregulation is achieved through GnRH-agonist, recombinant FSH 300 IU/d is given for 5 days, then the dose of recombinant FSH is adjusted according to ovarian response.

The clinical and ongoing pregnancy rate and other secondary outcome parameters are compared between these two groups.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Comparison of Mild Stimulation and Controlled Ovarian Stimulation in Poor Ovarian Responders: a Prospective Randomized Study.

Study Start Date :

Sep 1, 2013

Anticipated Primary Completion Date :

Sep 1, 2015

Anticipated Study Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mild ovarian stimulation Patients are stimulated with mild ovarian stimulation protocol,i.ed, from cycle day 3 to 7, letrozole 5mg per day are administrated and recombinant FSH 150 IU are given on day 4 and 6 . On cycle day 8, serum FSH LH, and estradiol levels are measured, and after then, the dose of recombinant FSH is adjusted according to the ovarian response and the maxim recombinant FSH dose is 150 IU/d. The GnRH-antagonist (Cetrotide) 0.25mg per day is administrated when the estradiol level reaches 200 pg/ml and the serum LH level rises above 2 times of basal LH level.	Other: mild stimulation protocol letrozole is used from cycle day 3 to 7 and low dose recombinant FSH(no more than 150 IU/d) is used on cycle day 4,6 and 8 onwards. GnRH antagonist is only applied in case of premature LH rise might happen. Other Names: letrozole recombinant FSH GnRH antagonist
Active Comparator: controlled ovarian stimulation Patients are stimulated using controlled ovarian stimulation protocol,i.e., from cycle day 18-22 (day 7 after ovulation) of previous cycle, all participants are given short-acting GnRH agonist (Triptorelin 0.05mg/d) for 14 days, then after checking serum FSH, LH and estradiol to make sure that complete downregulation is achieved, exogenous gonadotropin (recombinant FSH) 300 IU/d is given for 5 days, then the dose of recombinant FSH is adjusted according to ovarian response.	Other: controlled ovarian stimulation After fully downregulation by using short-acting GnRH agonist, 300 IU/d recombinant FSH is administrated for 5 days, then the dose is adjusted according to ovarian response. Other Names: GnRH agonist recombinant FSH

Arm

Intervention/Treatment

Experimental: mild ovarian stimulation

Patients are stimulated with mild ovarian stimulation protocol,i.ed, from cycle day 3 to 7, letrozole 5mg per day are administrated and recombinant FSH 150 IU are given on day 4 and 6 . On cycle day 8, serum FSH LH, and estradiol levels are measured, and after then, the dose of recombinant FSH is adjusted according to the ovarian response and the maxim recombinant FSH dose is 150 IU/d. The GnRH-antagonist (Cetrotide) 0.25mg per day is administrated when the estradiol level reaches 200 pg/ml and the serum LH level rises above 2 times of basal LH level.

Other: mild stimulation protocol

letrozole is used from cycle day 3 to 7 and low dose recombinant FSH(no more than 150 IU/d) is used on cycle day 4,6 and 8 onwards. GnRH antagonist is only applied in case of premature LH rise might happen.

Other Names:

letrozole

recombinant FSH

GnRH antagonist

Active Comparator: controlled ovarian stimulation

Patients are stimulated using controlled ovarian stimulation protocol,i.e., from cycle day 18-22 (day 7 after ovulation) of previous cycle, all participants are given short-acting GnRH agonist (Triptorelin 0.05mg/d) for 14 days, then after checking serum FSH, LH and estradiol to make sure that complete downregulation is achieved, exogenous gonadotropin (recombinant FSH) 300 IU/d is given for 5 days, then the dose of recombinant FSH is adjusted according to ovarian response.

Other: controlled ovarian stimulation

After fully downregulation by using short-acting GnRH agonist, 300 IU/d recombinant FSH is administrated for 5 days, then the dose is adjusted according to ovarian response.

Other Names:

GnRH agonist

recombinant FSH

Outcome Measures

Primary Outcome Measures

clinical pregnancy rate [7 weeks]

Secondary Outcome Measures

live birth rate [10 months]
Number of oocytes retrieved [3 weeks]
Number of transferrable embryo [3 weeks]
normal fertilization rate [3 weeks]
implantation rate [7 weeks]
ongoing pregnancy rate [3 months]
Total dose of recombinant FSH consumption [3 weeks]
length of stimulation [3 weeks]
serum estradiol level [3 weeks]
serum LH level [3 weeks]
serum progesterone level [3 weeks]
serum FSH level [3 weeks]
FSH level in follicular fluid [3 weeks]
LH level in follicular fluid [3 weeks]
Estradiol level in the follicular fluid [3 weeks]
progesterone level in follicular fluid [3 weeks]
testerone level in the follicular fluid [3 weeks]
anti-müllerian hormone (AMH)level in follicular fluid [3 weeks]
Ovarian Hyperstimulation Syndrome (OHSS) rate [7 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Poor ovarian responders b. Normal BMI (18-25 Kg/m2) c. Regular menstruation (with cycle 23-35 days)

Exclusion Criteria:

1. History of repeated IVF failure (previous IVF cycle >2) b. Serious adenomyosis c. Polycystic ovary syndrome(PCOS) patients d. History of allergic to ovulation induction medicines e. Abnormal uterine cavity, i.e, intrauterine adhesion f. Attending other clinical trials in the same period. g. History of systemic disease contradictory to COH or pregnancy.