Melatonin Study Between Diminished and Normal Responder in IVF

Study Overview
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Brief Summary
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Poor sleep quality may lead to increase in oxidative stress and free radicals which in turn may decrease the reproductive function. Many researchers have already proven improvement on reproductive function after antioxidant (melatonin) administration. The investigators wish to study the relationship between unexplained, young poor ovarian responder and oxidative stress.

Detailed Description
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Poor sleep quality may lead to increase in oxidative stress and free radicals which in turn may decrease the reproductive function. Many researchers have already proven improvement on reproductive function after antioxidant (melatonin) administration. The investigators wish to study the relationship between unexplained, young poor ovarian responder and oxidative stress. This is an randomized controlled trial to evaluate the effect of melatonin to improve the quality of sleep and reduce the oxidative stress. 100 patients will be randomized in to two groups, the one with melatonin administration for 2 weeks and the other with placebo administration. Each group will be composed of 2 sub groups, poor responders and normal responders. Then the serum and the follicular fluid will be collected at the time of oocyte retrieval and melatonin concentration oxidative stress marker will be measured.

Official Title
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Comparison of IVF Outcome and Endometrium Effect in Infertility Patients Between Diminished and Normal Ovarian Reserve After Melatonin Administration.

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: Melatonin adminstration
* Drug: placebo administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infertility patients visiting Bundang CHA hospital between the age of 20 to 40. Currently, not being treated for any gynecological or medical diseases. Exclusion Criteria: Current untreated pelvic pathology (moderate-to-severe endometriosis, submucosal uterine fibroids/polyps assessed by the treating specialist to affect fertility, pelvic inflammatory disease,uterine malformations, and hydrosalpinx.) Currently enrolled in another interventional clinical trial. Concurrent use of other adjuvant therapies (e.g.Chinese herbs, acupuncture). Autoimmune disorders. Undergoing preimplantation genetic diagnosis. Concurrent use of any of the following medications (Fluvoxamine,Cimetidine, Quinolones, Carbamazepine, rifampicin,Zolpidem, zopiclone, and other non-benzodiazepine hypnotic, other CYP1A2 inducers. Genetic disorders regarding galactose intolerance, lactase deficiency, glucose-galactose malabsorption Inability to comply with trial protocol.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: melatonin administration group<br>Total 50 patients are to be randomized into this group, 25 of which are poor responder and the others are normal responders. After randomization, participants are to under go melatonin administration intervention from the time of controlled ovarian hyperstimulation(COH) to the date of oocyte retrieval. If pregnancy is not confirmed in the first cycle, all subjects are to enter the second cycle after 1-2 months of recovery period. For the second cycle, the procedure will be repeated same as the first cycle with doubling of the drug dosage . It should also be administered for 2 weeks until the date of oocyte retrieval. | Drug: Melatonin adminstration<br>* The drug, melatonin will be taken every night from the time of COH to the date of oocyte retrieval. The method of administration is as follows: Melatonin 2mg once a day, 1 to 2 hours before bedtime for about 2 weeks until the date of oocyte retrieval.<br>|
| Placebo Comparator: placebo comparator<br>Total 50 patients are to be randomized into this group, 25 of which are poor responder and the others are normal responders. Participants for placebo comparator are advised to take the drug (placebo) from the time of COH to the date of oocyte retrieval. If pregnancy is not confirmed in the first cycle, all subjects are to enter the second cycle after 1-2 months of recovery period. For the second cycle, the procedure will be repeated same as the first cycle with doubling of the drug dosage . It should also be administered for 2 weeks until the date of oocyte retrieval. | Drug: placebo administration<br>* the drug, placebo pill will be taken every night from the time of COH to the date of oocyte retrieval. The method of administration is as follows: placebo pill once a day, 1 to 2 hours before bedtime for about 2 weeks until the date of oocyte retrieval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IVF outcome - oocyte quality | Evaluate oocyte quality on morphological standard as following category- Mature oocyte, Intermediate oocyte, atretic oocyte, post mature oocyte | 3 days after oocyte retrieval | 
| IVF outcome - embryo quality | grade the embryos& blastocysts according to the Lucinda Veeck & Gardner | 3 to 5 days after oocyte retrieval | 
| IVF outcome -biochemical pregnancy rate | serum human chorionic gonadotropin level>10 IU | on day 12 14 after embryo transfer | 
| IVF outcome - clinical pregnancy rate | presence of G-sac in the uterine cavity | at 6-8 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acquired oocyte No | number | 20weeks | 
| fertilization rate | ratio of no. of fertilized egg/ no of total retrieved eggs | 20weeks | 
| Comparing Pittsburgh sleep quality index | questionaires to evaluate the participants quality of the sleep. cut off : 13 points This questionaire is to be asked to the participants twice, before and after the administration of the drug | 20weeks | 
| marker(melatonin level, receptor, 8-OHdg) in serum, follicular fluid and endometrium during IVF | :pg/ml units are used | 20weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxidative stress, antioxidants, diminished ovarian reserve