Melatonin Study Between Diminished and Normal Responder in IVF

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

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.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Melatonin adminstration; Drug: placebo administration

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi Do
    • Seongnam si, Gyeonggi Do, Korea, Republic of, 13496
      • Bundang CHA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Infertility patients visiting Bundang CHA hospital between the age of 20 to 40.
2. Currently, not being treated for any gynecological or medical diseases.

Exclusion Criteria:

1. 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.)
2. Currently enrolled in another interventional clinical trial.
3. Concurrent use of other adjuvant therapies (e.g.Chinese herbs, acupuncture).
4. Autoimmune disorders.
5. Undergoing preimplantation genetic diagnosis.
6. Concurrent use of any of the following medications (Fluvoxamine,Cimetidine, Quinolones, Carbamazepine, rifampicin,Zolpidem, zopiclone, and other non-benzodiazepine hypnotic, other CYP1A2 inducers.
7. Genetic disorders regarding galactose intolerance, lactase deficiency, glucose-galactose malabsorption
8. Inability to comply with trial protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: melatonin administration group; 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; 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.
Placebo Comparator: placebo comparator; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bundang CHA Hospital
• Investigators: Principal Investigator: DONG HEE CHOI, M.D,Ph.D, BUNDANGCHA HOSPITAL

Publications and helpful links

General Publications

• Fernando S, Osianlis T, Vollenhoven B, Wallace E, Rombauts L. A pilot double-blind randomised placebo-controlled dose-response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol. BMJ Open. 2014 Sep 1;4(8):e005986. doi: 10.1136/bmjopen-2014-005986.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2017
• Primary Completion (Anticipated): August 30, 2019
• Study Completion (Anticipated): October 31, 2019

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: April 12, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: oxidative stress; antioxidants; diminished ovarian reserve
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 2016-07-013-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Study Protocol
   Information identifier: 31098

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No