N/A
N=2,370
Folic Acid and Zinc Supplementation Trial (FAZST)
Pregnancy · Live Birth · Spontaneous Abortion
Bottom Line
View on ClinicalTrials.gov: NCT01857310 ↗Enrolled (actual)
2,370
Serious AEs
0.5%
Results posted
Nov 2020
Primary outcome: Primary: Live Birth — 404; 416; 97; 91 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- 5 mg folic acid and 30 mg elemental zinc (Dietary_supplement); Placebo Comparator: Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Live Birth |
404; 416; 97; 91; 264; 277 | — |
| PRIMARY Semen Volume |
3.5; 3.5; 3.5; 3.5; 3.5; 3.5 | — |
| PRIMARY Sperm Concentration |
84.8; 89.0; 81.8; 76.1; 85.0; 92.2 | — |
| PRIMARY Sperm Motility |
52.7; 53.2; 51.7; 51.7; 52.5; 53.9 | — |
| PRIMARY Sperm Morphology |
5.7; 6.0; 5.2; 5.4; 5.6; 6.2 | — |
| PRIMARY DNA Fragmentation Index |
29.7; 27.2; 27.1; 26.8; 30.0; 27.0 | — |
| PRIMARY Total Motile Sperm Count |
183; 182; 165; 152; 186; 188 | — |
| SECONDARY Human Chorionic Gonadotropin (hCG) Detected Pregnancy (Implantation) |
479; 490 | — |
| SECONDARY Clinical Intrauterine Pregnancy |
449; 462 | — |
| SECONDARY Ectopic Pregnancy |
6; 5 | — |
| SECONDARY Early Pregnancy Loss |
137; 150 | — |
| SECONDARY Preeclampsia or Gestational Hypertension |
47; 51 | — |
| SECONDARY Gestational Diabetes |
26; 34 | — |
| SECONDARY Cesarean Delivery |
143; 129 | — |
| SECONDARY Preterm Delivery |
67; 45 | — |
| SECONDARY Small for Gestational Age |
62; 59 | — |
| SECONDARY Gestational Age |
38.6; 38.8 | — |
| SECONDARY Birth Weight |
3062; 3133 | — |
| SECONDARY Stillbirth |
1; 4 | — |
| SECONDARY Neonatal Mortality |
3; 2 | — |
| SECONDARY Major Neonatal Complications |
2; 1 | — |
| SECONDARY Structural Malformations |
15; 14 | — |
| SECONDARY Severe Maternal Morbidity |
15; 10 | — |
| SECONDARY Fertilization Rate Per Cycle, % |
75.3; 77.7 | — |
| SECONDARY Number of Good Quality Embryos on Day 5 Per Cycle |
2.66; 2.98 | — |
| SECONDARY Percentage of Good Quality Embryos on Day 5 Per Cycle |
17.2; 18.5 | — |
| SECONDARY Number of Embryos Transferred Per Cycle |
1.50; 1.51 | — |
| SECONDARY Number of Embryos Cryopreserved Per Cycle |
4.22; 4.32 | — |
| SECONDARY Sperm Penetration Per Cycle, % |
62.7; 74.8 | — |
| SECONDARY Cells on Day 3 Per Embryo Per Cycle |
5.60; 5.98 | — |
| SECONDARY Cells on Day 3 Per Embryo Per Cycle, Categorical |
0.27; 0.22; 0.73; 0.78 | — |
| SECONDARY Cells on Day 5 Per Embryo Per Cycle, Categorical |
0.20; 0.19; 0.80; 0.81 | — |
| SECONDARY Embryo Morphology on Day 3 Per Cycle, Categorical |
0.66; 0.68; 0.34; 0.32 | — |
| SECONDARY Embryo Morphology on Day 5 Per Cycle, Categorical |
0.28; 0.35; 0.72; 0.65 | — |
| SECONDARY Method of Fertilization Per Cycle |
0.74; 0.79; 0.26; 0.21 | — |
| SECONDARY Quality of Embryos Transferred Per Cycle, Categorical |
0.75; 0.73; 0.25; 0.27 | — |
| SECONDARY Chromosomal Complement of Embryo Per Cycle |
0.75; 0.32; 0.25; 0.68 | — |
Summary
The overarching goal of this trial is to determine if an intervention comprising folic acid and zinc dietary supplementation improves semen quality and indirectly fertility outcomes (i.e., live birth rate) among couples trying to conceive and seeking assisted reproduction. The following study objectives underlie successful attainment of the overarching research goal:
1. To estimate the effect of folic acid and zinc dietary supplementation on semen quality parameters, including but not limited to concentration, motility, morphology, and sperm DNA integrity, relative to the placebo group.
2. To estimate the effect of folic acid and zinc dietary supplementation on fertility treatment outcomes [fertilization, embryo quality, implantation/human Chorionic Gonadotropin (hCG) confirmed pregnancy, clinical pregnancy, live birth], relative to the placebo group.
3. To estimate the association between semen quality parameters, sperm DNA integrity and fertility treatment outcomes (fertilization, embryo quality, clinical pregnancy, live birth) and to identify the best combination of semen quality parameters for prediction of clinical pregnancy and live birth.
4. To estimate the effect of folic acid and zinc dietary supplementation on fertilization rates among couples undergoing assisted reproductive technology procedures, relative to the placebo group.
5. To estimate the effect of folic acid and zinc dietary supplementation on embryonic quality among couples undergoing assisted reproductive technology procedures, relative to the placebo group.
Eligibility Criteria
Couples Inclusion Criteria:
- Heterosexual couples in a committed relationship with a female partner aged 18-45 years and male partner aged 18 years and older attempting to conceive and seeking assisted reproduction at participating fertility clinics.
- Couples actively trying to conceive.
- Couples who are planning ovulation induction (OI), natural fertility optimization methods, or intrauterine insemination (IUI) should be willing to be on the study dietary supplement for at least 3 weeks before starting the next assisted reproduction cycle.Women with regular periods may initiate their fertility therapy at the start of the woman's menstrual cycle following randomization if randomization occurred within the first 10 days of the cycle, but must wait one menstrual cycle if the visit occurred after day 10 of the cycle). For women with irregular periods or amenorrhea, the male must be on the study supplement for 3 weeks prior to initiation of any ovulation induction medication (e.g., clomid, letrozole, gonadotropins).
Couples Exclusion Criteria:
- Female partner unwilling to participate (e.g., no abstraction of her assisted fertility treatment record or unwilling to complete baseline visit).
- Couples using donor, cryopreserved sperm, or sperm obtained via microsurgical or percutaneous epididymal sperm aspiration.
- Couples attempting to conceive with a gestational carrier (surrogate).
- Positive urine pregnancy test at screening.
Male Inclusion Criteria:
- Willing to provide semen samples according to the proposed schedule at baseline, 2, 4, and 6 months of follow-up.
- Able to complete regular study questionnaires and daily journals aimed at capturing ejaculation, sexual intercourse and lifestyle factors considered to affect male fecundity (e.g., cigarette smoking, fever, high temperature environment and other environmental exposures) and other data collection instruments (e.g., physical activity, food frequency questionnaire, stress).
Male Exclusion Criteria:
- Age 45 years.
Data sourced from ClinicalTrials.gov (NCT01857310). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.