Clinical trial NCT03714009: Effect of Fasting on ICSI Outcomes in Poor Responders
Official title: Effect of Fasting on ICSI Outcomes in Poor Responders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: Infertility
Poor ovarian reserve
Intracytoplasmic sperm injection
fasting
Lead sponsor: Kasr El Aini Hospital
Sponsor class: OTHER
First posted: 2018-10-22
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study is a prospective, randomized controlled trial conducted at the In Vitro Fertilization ( IVF) center of the Department of Obstetrics \& Gynecology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Egypt, from October 2018 to September 2019, to determine the clinical effect of fasting on ICSI outcomes in poor responders 360 participants will be randomized withdrawing closed envelopes for each patient into group A and group B .

Group (A): patients will have periodic fasting for 4 weeks prior to the treatment cycle. The fasting method involves daily fasts of 14-16hours and restrict eating to an 8-10 hour "eating window" as 2-3 or more meals of balanced diet. Group (B): no fasting, patients will have usual balanced diet as 3 meals and 2 snacks all over the day. Both groups should take adequate water and non calorie beverages intake daily (2-3 liters).

All patients will start the ICSI cycle using the same treatment protocol. Primary outcome is clinical pregnancy rate per cycle. Secondary outcomes include Body mass index (BMI) and waist/hip ratio (WHR), fasting insulin , fasting plasma glucose, Homeostatic model assessment (HOMA) index, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL), AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2, Days of stimulation , dose of gonadotrophins, number of M II oocytes retrieved, number of grade1and 2 embryos, number of frozen embryos, freeze all cycles, Ovarian Hyperstimulation syndrome (OHSS), Chemical pregnancy rate, clinical pregnancy, twins, abortion, ectopic pregnancy, preterm labour, live birth rate

Detailed description: This study is a prospective, single-blinded (to the outcomes assessor), randomized controlled trial conducted at the In Vitro Fertilization ( IVF) center of the Department of Obstetrics \& Gynecology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Egypt, from October 2018 to September 2019, to determine the clinical effect of fasting on ICSI outcomes in poor responder patients. Ethical committee approval was obtained. The study will include 360 infertile patients with poor ovarian reserve (POR )diagnosed by low Antral follicle count (AFC)( less than 5 follicles), Elevated basal follicle-stimulating hormone (FSH) (more than 10 IU/mL) and low anti-Mullerian hormone (AMH)(less than 1.5 ng/ml), previous POR (≤three oocytes with a conventional stimulation protocol). Women with diabetes, thyroid disorder or other endocrine dysfunctions, uterine abnormalities were excluded.Also severe oligo-astheno-teratozoospermia or azospermia are excluded.

All patients are informed about the study and consent is given by those who accept to participate.

Careful history taking include infertility type, duration , cause, obstetric history, medical and surgical history and demographic distribution is taken. Full physical examination and 2 dimensional (2D) transvaginal sonography (TVS) are done on day 2 to 5 of menses to assess antral follicle count, uterus and adnexa . Body mass index (BMI) and waist/hip ratio (WHR) are calculated, Blood samples are taken for fasting plasma glucose, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL),AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2) All 360 participants will be randomized withdrawing closed envelopes for each patient into group A and group B .

Group (A): patients will have periodic fasting for 4 weeks prior to the treatment cycle. The fasting method involves daily fasts of 14-16hours and restrict eating to an 8-10 hour "eating window" as 2-3 or more meals of balanced diet. Group (B): no fasting, patients will have usual balanced diet as 3 meals and 2 snacks all over the day. Both groups should take adequate water and non calorie beverages intake daily (2-3 liters) Subjects are instructed to wait for spontaneous menses. The next visit is scheduled on day 2 of next cycle when transvaginal ultrasound is done to confirm that endometrial thickness \<5mm, no ovarian cyst by ultrasound. Body mass index (BMI) and waist/hip ratio (WHR) are calculated. Blood samples are taken for fasting plasma glucose, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL), AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2),and then antagonist protocol is followed. Gonadotropins as Intramuscular (I.M.) injections of 150-300 (International units) I.U. of highly purified Human Menopausal Gonadotropins daily (Merional, 75 I.U. /vial, IBSA). and Urofollitropin or highly purified human follicle stimulating hormone(Fostimon®, 75 I.U. /vial, IBSA) are give in a ratio of 1:1.The dose is adjusted according to the age, BMI, Antral follicle count (AFC), serum levels of AMH, FSH and ovarian response.

On the sixth day of stimulation , a visit is scheduled to assess the ovarian response ( folliculometry) by TVS. Gonadotrophin releasing hormone antagonist (GnRH antagonist) which is Cetrorelix 0.25mg ( Cetrotide®, 0.25 mg/ vial, Merck Serono, is filled and mixed with diluent from a prefilled syringe with a 20 gauge needle) is given subcutaneously (S.C.) by 27-gauge needle starting from the 6th day of stimulation (fixed antagonist protocol).

Next visits are every other day for follow up using the TVS. The trigger by Human Chorionic Gonadotrophin (HCG)10000 I.U., I.M. ( Pregnyl, Organon) is given when at least 3 follicles reach 18mm in mean diameter or more and E2 level is less than 2500 pg/ml. Ovum retrieval is done 34 hours after HCG injection and embryo transfer using Wallace catheter on day 2 to 3. Luteal support includes natural Progesterone 400 mg 1x2 as rectal suppository, Folic acid 0.5 mg orally once daily, Amoxicillin-Clavulanic Acid 1gm 1x2x7 orally, Progesterone 100 I.M. injections daily for 10 days, Acetylsalicylic Acid (75 mg) orally once daily Quantitative ß- HCG in serum after is done after 14 days of embryo transfer.TVS is performed to detect clinical pregnancy at 6-7 weeks of gestation.

Primary outcome is clinical pregnancy rate per cycle. Secondary outcomes include Body mass index (BMI) and waist/hip ratio (WHR), fasting plasma glucose, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL), AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2, Days of stimulation , dose of gonadotrophins, number of M II oocytes retrieved, number of grade1and 2 embryos, number of frozen embryos, freeze all cycles, Ovarian Hyperstimulation syndrome (OHSS), Chemical pregnancy rate, clinical pregnancy, twins, abortion, ectopic pregnancy, preterm labour, live birth rate

Eligibility criteria: The study will include:

infertile patients with poor ovarian reserve (POR )diagnosed by low Antral follicle count (AFC)( less than 5 follicles), Elevated basal follicle-stimulating hormone (FSH) (more than 10 IU/mL) and low anti-Mullerian hormone (AMH)(less than 1.5 ng/ml), previous POR (≤three oocytes with a conventional stimulation protocol).

Women with diabetes, thyroid disorder or other endocrine dysfunctions, uterine abnormalities were excluded.Also severe oligo-astheno-teratozoospermia or azospermia are excluded.

Primary outcomes:
measure: clinical pregnancy rate per cycle
timeFrame: 10 weeks
Secondary outcomes:
measure: Body mass index
timeFrame: 4 weeks of fasting
measure: Waist/Hip ratio
timeFrame: 4 weeks of fasting
measure: Number of days of stimulation with gonadotrophins
timeFrame: 6 weeks
measure: Number of ampoules of gonadotrophins
timeFrame: 6 weeks
measure: number of M II oocytes retrieved
timeFrame: 6 weeks
measure: number of grade1and 2 embryos
timeFrame: 6-7 weeks
measure: number of frozen embryos
timeFrame: 6-7 weeks
measure: number of freeze all cycles
timeFrame: 6 weeks
measure: number of cancelled cycles
timeFrame: 6 weeks
measure: Rate of chemical pregnancy rate
timeFrame: 10 weeks
measure: Rate of twin pregnancy
timeFrame: 10 weeks
measure: Rate of abortion per cycle
timeFrame: 10-24 weeks after embryo transfer
measure: Rate of ectopic pregnancy
timeFrame: 10 weeks
measure: Rate of preterm labour
timeFrame: After 24 weeks of start of study
measure: live birth rate
timeFrame: After40 weeks of start of study
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: KasrELAiniH
Study officials:
affiliation: KasrAlainiH
name: Amira S Dieb, MD
role: PRINCIPAL_INVESTIGATOR
References: