What Supplements or Vitamins Should I Take for IVF?

Which are the best supplements/vitamins for improving egg quality or improving chances with IVF?

Written by: Taylor J. Graber MD

Medically Reviewed by: Aimee Eyvazzadeh MD

ASAP IVs has worked with many patients at different points of the fertility journey, helping to reduce inflammation, reduce free radicals, improve egg quality, and eventually help mitigate the challenges with infertility.

Women are born with a finite amount of eggs which can be utilized later in life to become fertilized (by a sperm), become an embryo, implant in the uterus, eventually develop into a fetus, and 40 weeks later be delivered as a healthy breathing baby!

The quantity of these eggs is determined at birth. During each menstrual cycle (approx.. 28-30 days), typically one egg matures for ovulation and a small number of other eggs are “used up” when they are do not mature, and the finite egg count decreases. The quality of a woman’s eggs also changes as she ages. The number of quality eggs (those considered genetically “normal” or containing the proper amount of chromosomes, or “euploid”) is reduced with age. Female fertility peaks at approximately age 25,  and begins to decline rapidly after 35 years of age. Dramatic changes in both quantity and quality of eggs occur between 35-40 years old, resulting in reduced ovarian reserve for a woman. Unfortunately, as the number of quality eggs is reduced, the chances of successfully conceiving are reduced, even with assisted reproductive technologies such as Intrauterine Insemination or In-Vitro fertilization (IVF). Menopause occurs when there is no longer a sufficient egg reserve to ovulate each month.

In recent years, women in our population are statistically waiting longer to have families. With this, the incidence of infertility (described as the inability to become pregnant after 1 year of trying to conceive) has increased as well. IVF utilizes medication to increase the number of mature eggs that are available to be fertilized each month. These eggs are extracted and then combined with sperm in a lab to hopefully produce embryos, which are then frozen for later use or transferred to a woman’s uterus a short time after. While a higher number of eggs able to be retrieved is favorable, quality of the eggs is very critical for successful creation of viable embryos. It is important to be aggressive in maximizing the quality of eggs when they are needed, both in a natural conception environment, and more especially for IVF. Egg quality is difficulty to change as a woman’s age increases, though there is plenty of data to support various lifestyle changes for improvements in egg quality. One of these lifestyle changes that can be beneficial is the addition of certain supplements to the diet.

Of note, eggs take about 90 days to develop and mature prior to use within a menstrual cycle. It is therefore recommended to start taking these supplements as early as possible when considering improving fertility outcomes. Many fertility experts recommend starting these supplements >90 days before trying to conceive, when possible.

CoQ10

Mitochondria are organelles located in the cells of the body, are the “powerhouse of the cell”, and are responsible for utilizing oxygen to move electrons and generate energy (which is the creation of adenosine triphosphate or ATP). Coenzyme Q10 (CoQ10) is an antioxidant and aids in the process of creating ATP via the electron transport chain in the mitochondria. It is part of the mitochondrial inner membrane. When CoQ10 levels are higher, the electron transport chain can more efficiently function to create energy. When more energy is produced by the mitochondria, cells with a higher metabolic requirement (such as eggs and sperm) can more effectively function and develop.

Oxidative stress (free radical damage of cells and DNA) is a proposed mechanism which decreases female fertility. Levels of CoQ10 naturally decrease as you age. Taking anti-oxidants such as COQ10 can help reduce this damage and improve outcomes. Various studies have looked at this, such as the following:

Study: Does coenzyme Q 10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials by Florou et. al (October 2020) [1].

Methods: Systematic review article reviewing 5 randomized controlled trials in Pubmed, Cochrane, and Scopus with 449 infertile women (215 in CoQ10 group and 234 in placebo group).

Results: Supplementation with CoQ10 increased clinical pregnancy rates compared to placebo (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30-4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding live birth rates (OR 1.67, 95% CI 0.66-4.25, p = 0.28; I2 34%) and miscarriage rates (OR 0.61, 95% CI 0.13-2.81, p = 0.52; I2 0%).

Conclusions: Oral supplementation of CoQ10 may increase clinical pregnancy rates without an effect on live birth rate or miscarriage rates.

Our take: Infertility experts like Dr. Aimee Eyvazzadeh recommend taking between 600–900 grams of CoQ10 per day. This can be in the form of Ubiquinone (the oxidized form) and Ubiquinol (the reduced and active form). The more potent form is called Ubiquinol. This supplement may help the mitochondria increase ATP production, create more energy, improve egg quality, and improve clinical pregnancy rates (the most important outcome after all!).

Vitamin D

Vitamin D (also called “calciferol”) is a fat-soluble vitamin which is naturally present in few foods and is available to take as a dietary supplement [through D2 (ergocalciferol) and D3 (cholecalciferol)]. It is also produced in the body (endogenously) through the conversion of sunshine on the skin (through ultraviolet (UV) rays), which triggers the Vitamin D synthesis pathway. Vitamin D which is obtained through sun exposure and supplementation is biologically inactive and must undergo several physiologic changes (hydroxylations) to convert Vitamin D to 25-hydroxyvitamin D called 25(OH)D (called calcidiol) in the liver, and then to 1,25-dihydroxyvitamin D called 1,25(OH)2D called calcitriol. This is the active form of Vitamin D in the body. This active form of Vitamin D promotes calcium absorption in the gut, regulates bone remodeling and mineralization, and maintains proper serum levels of calcium and phosphate.

Vitamin D deficiency is very common in most countries. A systematic review has shown that 25(OH)D concentrations below 50 and 25 nmol/L during pregnancy were reported in 64% and 9% of Americans, and 57% and 23% of Europeans, and is highest during the winter months (Pilz). There is data suggesting that low blood levels of Vitamin D may negatively impact fertility, pregnancy outcomes, and lactation (Pilz). This has been shown in several studies, including the following Meta-Analysis of Randomized Controlled Trials (Chu 2018).

Study: Is serum vitamin D associated with live birth rates in women undergoing assisted reproductive therapy (ART)? (Chu 2018)

Methods: Systematic review and meta-analysis of 11 cohort studies including 2700 women, analyzing relationship between Vitamin D levels and assisted reproductive therapy outcomes.

Results: Live birth rate was more likely in women with higher Vitamin D levels compared to those with lower Vitamin D levels (OR 1.33 [1.08-1.65]). Five studies (including 1700 patients) found that women replete in vitamin D were more likely to achieve a positive pregnancy test than women deficient or insufficient in vitamin D (OR 1.34 ([1.04-1.73]). Clinical pregnancy was found to be more likely in women replete in vitamin D (OR 1.46 [1.05-2.02]). There was no association found between miscarriage and vitamin D concentrations (OR 1.12 [0.81-1.54].

Conclusions: Vitamin D deficiency and insufficiency can be an important condition which decreases success rate in women trying to conceive and undergoing ART.  

When looking at all available evidence derived from published studies, it appears that Vitamin D supplementation in women trying to conceive is safe, improves Vitamin D and calcium levels in the blood, and protects skeletal health. Randomized controlled trials suggest beneficial effects of Vitamin D supplementation and improved pregnancy and neonatal outcomes, and the serum levels of importance seem to be 25(OH)D of <50 nmol/L or >75 nmol/L.

Note: A meta-analysis documented that early spontaneous pregnancy loss was significantly increased in women with serum 25(OH)D concentrations below 50 nmol/L compared to those with higher 25(OH)D levels (relative risk (RR): 2.24; 95% CI: 1.15 to 4.37. A study in 1191 women with previous pregnancy losses showed that women with serum 25(OH)D concentrations ≥75 nmol/L preconception were more likely to achieve clinical pregnancy (adjusted RR: 1.10; 95% CI: 1.01 to 1.20) and livebirth (RR: 1.15; 95% CI: 1.02 to 1.19) compared to those with lower serum 25(OH)D concentrations.

Our take:

Guidelines suggest a daily Vitamin D intake of 400-2000 IU in order to maintain 25(OH)D concentrations of 50-75nmol/L. We recommend a daily Vitamin D intake of 1000-2000 IU to maintain a serum level in this ideal range. If an intramuscular injection is preferred over daily supplement injection (or a quick catch-up period is desired), then a once monthly injection of 50-100k IU is performed every 4 weeks. This recommendation is based on studies showing that an injection of 100k IU peaks at 4 weeks, and then begins to taper (Gorman 2017). Again, it is best to start these supplements >90 days prior to trying to conceive for them to have optimal effects.

Melatonin

Melatonin is a hormone produced in the brain, in a small tissue called the pineal gland. It plays an important role in nocturnal maintenance of the circadian rhythm and regulating the sleep-wake cycle (,when to go to sleep and when to wake up). Melatonin protects against age-related mitochondrial oxidative damage. Similar to CoQ10, the action is in the mitochondria, helping to reduce the risk of mitochondrial oxidative damage by free radicals in the ovaries. Also similar to CoQ10, Melatonin supplementation has been shown to have a beneficial effect on fertility rates through improving egg quality.

Study: Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment (Espino 2019)

Methods: Randomized controlled trial of 40 patients into 4 groups. Group 1 was normal fertility. Group 2 was unexplained infertility (UI) with no melatonin supplementation, Group 3 was UI with 3mg melatonin, and Group 4 was UI with 6mg melatonin. Supplements were started on the first appointment of controlled ovarian stimulation until the day of follicular puncture/egg retrieval.

Results: A total of 86 (8.7 ± 1.5) and 68 (6.8 ± 1.2) oocytes were retrieved in group 1 (fertile women) and group 2 (UI patients), respectively (Table 2). While the maturation, fertilization, and embryonic development in UI patients were similar to those in fertile women, the pregnancy rates in fertile women were higher (50.0% (5/10)) than that of UI patients (20.0% (2/10)). Importantly, administration of melatonin to UI patients significantly (p < 0.05) enhanced the number of oocytes retrieved, irrespective of the dose of melatonin (10.0 ± 1.7 and 9.5 ± 2.1 in group 3 and group 4, respectively; Table 2). The proportion of mature oocytes (83.6% in group 3), the percentage of fertilized oocytes (67.4% and 63.7% in group 3 and group 4, respectively), and the average number of transferable embryos (5.1 ± 1.1 and 4.6 ± 0.8 in group 3 and group 4, respectively) were significantly (p < 0.05) higher in UI patients treated with melatonin. Consequently, the number of pregnancies per embryo transfer in those groups treated with melatonin were relatively higher (30.0% (3/10)) compared to those found in UI patients (20%).

Conclusions:  Melatonin supplementation re-balanced the intrafollicular oxidative status, improved oocyte quality, and slightly enhanced IVF success rates in UI patients. As both doses of the melatonin tested were effective, this suggests that the lower dose (3 mg/day) is sufficient to ameliorate the harmful microenvironment in the follicular fluid of such patients and hence, improve their oocyte quality. 

Our take:

Melatonin supplementation at both 3mg per day and 6mg per day showed beneficial effects in number of eggs retrieved, number of eggs that were mature, number fertilized, number of transferrable embryos, and a trend towards increased pregnancies per embryo transfer.  Melatonin has a mild side effect profile and can be helpful as a sleep aid. For this reason, we recommend supplementing with Melatonin 3mg per day, taken nightly before bed starting 60-90 days before beginning IVF or trying to conceive.

Acai Berry

Acai powder is rich in antioxidants, which can help reduce free radical damage to the ovaries and to eggs, improve egg quality, and can improve outcomes. Acai can be obtained through acai bowls or through supplementation.

Study: OVAHealth Study

Methods: Cohort study of 138 patients taking Acai supplements for 8-12 weeks prior to undergoing IVF.

Results: A total of 138 patients were included in the study. Participants showed significant improvements in clinical outcomes for participants (n=138) that took the acai supplements for 8-12 weeks prior to their IVF cycle, as compared to their previous IVF cycle (without acai), including higher number of eggs (17.4 ±10.1 vs. 13.7±8.2; P=0.0001), fertilized embryos (9.7±6.2 vs. 7.3±4.8; P=0.0001) and chromosomally normal blastocysts (43.6% vs. 30.3%; P=0.0001). Outcomes after transfer of a chromosomally normal blastocyst for these 138 patients all with prior IVF failures were excellent: 80.4% clinical pregnancy with fetal heart tone, 5.4% miscarriage rate and 76.1% live birth rate.

Conclusions:  Supplementation with acai supplements for 8-12 weeks prior to undergoing IVF showed improvements in total egg number, fertilized embryos, and chromosomally normal blastocysts. 

Our take:

Acai is an effective (and tasty!) supplement which can help improve a number of IVF parameters, and can be another helpful adjunct for IVF. Supplementation should begin 8-12 weeks (again, try for >90 days) before IVF.

NAD

NAD+ (nicotinamide adenine dinucleotide) is an enzyme consisting of adenine and nicotinamide. Most importantly, it is involved in critical steps of the electron transport chain in the mitochondria (like CoQ10) responsible for generating energy (ATP). It also is an important signaling molecule which can effect cellular transcription of proteins and DNA repair. As we age, egg quality decreases in step with declining levels of NAD+. Proposed benefits of NAD+ supplementation (often through the metabolic precursor nicotinamide mononucleotide or NMN) include improving egg quality, restoring fertility potential, and rescue reproductive capability.

Study: NAD+ Repletion Rescues Female Fertility during Reproductive Aging (Bertoldo et al. 2020).

Methods: Animal study on mice, supplementing the diet with NMN. They supplemented mice with 2g/L NMN for 4 weeks.

Results: NAD(P)H levels declined in the eggs of aged mice, but not in the ovary. NMN supplementation increased NAD+ levels in the whole of the ovary. Oocytes (eggs) from mice treated with NMN had a larger diameter (which may be relevant given that oocytes with smaller diameters are associated with poorer outcomes following IVF), trended towards improved blastocyst formation rates. Length of NMN treatment correlated with improvements in inner cell mass size (which is highly predictive of pregnancy success). Embryos cultured in the presence of NMN showed improved blastocyst formation in embryos from ages females, but not in young females. Offspring of mothers treated with an NMN diet showed no signs of physiological or behavioral changes, other than a small increase in lean body mass. This is in line with other data showing NAD+ supplementation during lactation/breastfeeding is not harmful and may be beneficial for offspring.

Conclusions:  This study was on mice, not on humans, but showed that NAD(P)H levels decline with age, and NAD+ repletion using NMN restores egg quality, enhances ovulation rate, and improves fertility. Separately, embryos cultured in a medium containing NMN can have reductions in age related detriments. NAD+ benefit may be related to improved energy supply, in high demand cells such as oocytes undergoing cellular division for reproduction.

Our take:

As this study was performed on mice, there are crossover studies with humans which need to be performed to determine optimal dosing, frequency, and duration. NAD+ can be supplemented in oral, intramuscular, and intravenous formulations. Our recommendation is to start an oral supplement, in 150mg or 300mg dosage daily as tolerated, starting >90 days before trying to conceive. When starting <90 days from IVF, IV or IM formulations of NAD+ can be helpful. These formulations can more directly increase NAD+ levels in the body and achieve optimal serum concentrations more quickly. We recommend 250 to 500mg IV weekly for 4-6 weeks before IVF, along with continuing oral supplementation. Like any supplement, if you experience any significant side effects (such as headaches, flushing, chest palpitations, or worsening anxiety), please stop taking them.

Dehydroepiandrosterone (DHEA)

DHEA is a hormone which is naturally produced in the body by the adrenal glands and can also be taken as a supplement. Through several reactions, DHEA is converted to Estrone and Estradiol (Estrogen), which is important in follicle/oocyte development. A diagram showing DHEA is shown below.

One of the proposed benefits for DHEA is in patients with Diminished Ovarian Reserve (DOR). When encountering DOR, it is recommended to take an aggressive approach with maximizing anti-oxidant supplements as well as available supplements/treatments to improve oocyte quality and improve chances of a successful outcome. Proposed benefits include increase egg count, egg quality, and improving pregnancy outcomes. A meta-analysis looking at DHEA in DOR is shown below.

Study: The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis (Qin 2016).

Methods: Meta-analysis of 9 various studies (4 randomized controlled trials, four retrospective studies, and one prospective study) including 540 cases and 688 controls.

Results: Pooled analysis showed that clinical pregnancy rates were increased significantly in DOR patients who were pre-treated with DHEA (OR=1.47, 95% CI: 1.09-1.99), whereas no differences were found in the number of oocytes retrieved, the cancellation rate of IVF cycles and the miscarriage rate between the cases and controls (WMD= -0.69, 95% CI: -2.18-0.81; OR=0.74, 95% CI: 0.51-1.08; OR=0.34, 95% CI: 0.10-1.24). However, it is worth noting that when data were restricted to RCTs, there was a non-significant difference in the clinical pregnancy rate (OR=1.08, 95% CI: 0.67-1.73). We concluded that DHEA supplementation in DOR patients might improve the pregnancy outcomes.

Conclusions:  DHEA supplementation in women with diminished ovarian reserve (DOR) patients might improve the pregnancy outcomes.

Our take:

DHEA can be a helpful adjunct for increasing pregnancy success in women with Diminished Ovarian Reserve. However, taken in excess or for too long, DHEA can result in a high level of serum testosterone which can be harmful for successful egg product, which is a definable negative side-effect. For this reason, we recommend that before starting DHEA independently, you discuss taking it with your IVF doctor to determine if it is the best supplement for you. Some of these decisions involve checking baseline serum labs for levels of DHEA and Testosterone, and then re-checking them after 6-8 weeks of starting the supplement. Signs of increasing serum testosterone include acne (on the face or on the back) or increasing hair growth (often in new places that you haven’t noticed it before), which can be an indication that serum levels of testosterone need to be checked and that treatment may need to be stopped.

Myo-Inositol and Inositol

Myo-inositol is a vitamin present in a number of foods (fruits, beans, grains, seeds), and has been recently studied as an additive supplement to improve fertility outcomes (namely in polycystic ovarian syndrome). It is available as an over-the-counter dietary supplement and does not require a prescription. It appears safe and non-toxic when taken in recommended dosage amounts (2 grams or 2000mg twice daily, taken with 200 micrograms of Folic acid twice daily). It can help reduce testosterone levels and improve insulin resistance (which is helpful in PCOS). It also has proposed benefits including the improvement of oocyte and embryo quality as well as improved pregnancy rates.

Study: Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET (Zheng 2017)

Methods: Meta-analysis and systematic review of 7 trials with 935 total women.

Results: Myoinositol supplement was associated with significantly improved clinical pregnancy rate [95% confidence interval (CI), 1.04–1.96; P = .03], reduced abortion rate (95% CI, 0.08–0.50; P = .0006), increased the proportion of Grade 1 embryos (95% CI, 1.10–2.74; P = .02), decreased the proportion of poor quality oocytes (95% CI, 0.11–0.86; P = .02), and reduced the total amount of ovulation drugs required for IVF (95% CI, –591.69 to –210.39; P = .001). There were no significant differences in total oocytes retrieved, MII stage oocytes retrieved, stimulation days, and E2 peak level.

Conclusions:  Myoinositol supplement increase clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. It may improve the quality of embryos, and reduce the unsuitable oocytes and required amount of stimulation drugs.

Our take:

Myo-inositol is a low risk supplement which appears to improve oocyte quality, improve the quality of embryos produced by IVF, and can potentially reduce the dosage of drugs needed for IVF stimulation. There are multiple studies which have shown benefit with myo-inositol when treating PCOS. We recommend this as a supplement (2000mg or 2grams) taken with folic acid (200 micrograms) twice daily, after consultation with your IVF doctor. It is beneficial to start earlier as opposed to later, ideally >90 days before IVF or trying to conceive.

Pterostilbene

Pterostilbene is a closely related to resveratrol, and is an anti-oxidant (commonly found in grapes). It has proposed benefits for anti-aging, anti-oxidant, and anti-inflammatory benefits, as well as insulin sensitization. Recently, it has been proposed to be of fertility benefits, including women with diminished ovarian reserve, polycystic ovary syndrome, and endometriosis. We looked at two recent articles analyzing the risks and benefits of taking Resveratrol for fertility.

Study: Preconception resveratrol intake against infertility: Friend or foe? (Ochiai 2020).

Methods: Literature review

Results: Resveratrol upregulates sirtuin (SIRT)1 expression in ovaries, which is associated with protection against oxidative stress. It leads to the activation of telomerase activity and mitochondrial function, improving ovarian function. In the endometrium, resveratrol downregulates the CRABP2-RAR pathway leading to suppressing decidual and senescent changes of endometrial cells, which is essential for embryo implantation and placentation. Moreover, resveratrol may also induce deacetylation of important decidual-related genes.

Conclusions:  Resveratrol has potential therapeutic effects for improving ovarian function; however, it also has anti-deciduogenic actions in uterine endometrium. In addition, its teratogenicity has not yet been ruled out; thus, resveratrol should be avoided during the luteal phase and pregnancy.

 Study: Influence of resveratrol supplementation on IVF-embryo transfer cycle outcomes (Ochiai 2019).

Methods: Single center, cross-sectional retrospective study looking at resveratrol supplementation (200mg/day) and influence on IVF embryo transfer outcomes. There were two groups, the reserveratrol group (given the supplement, 102 women and 204 cycles) and the non-resveratrol group (not given the supplement, 2958 women and 7073 cycles).

Results: After matching patients by age at the time of oocyte retrieval, grade and developmental stage of embryos, number of embryos transferred, and fresh or vitrified-warmed embryo transfer, multivariate logistic regression analysis showed that resveratrol supplementation is strongly associated with a decrease in clinical pregnancy rate [odds ratio (OR) 0.539, 95% confidence interval (CI) 0.341-0.853] and an increased risk of miscarriage (OR 2.602, 95% CI 1.070-6.325).

Conclusions:  Resveratrol supplementation during embryo transfer cycles appears to be detrimental for pregnancy outcomes.

Our take:

Resveratrol has potential benefits for improving ovarian function, which can potentially improve oocyte production, oocyte quality, and embryo quality. However, this appears to come at the cost of reducing endometrial performance at the stage of implantation of an embryo. Most apparent benefits would include taking this as a supplement when trying to increase embryo production, and then stopping supplement at a time before the process of embryo transfer. Here is a diagram from the authors of the above paper:

Vitamin C (Ascorbic Acid)

Ascorbic Acid, also called Vitamin C, is a water-soluble vitamin essential for the formation of collagen (famously to help prevent scurvy!) and is an anti-oxidant with many uses in the body. It is used to maintain and repair tissues, produce neurotransmitters, and functions as a critical cofactor in many enzymatic reactions. Most animals can synthesize their own Vitamin C, but humans and apes are unable to, and must obtain Vitamin C from dietary sources (eat your citrus!). It is also available as a generic, over-the-counter supplement, and is obtained in most multi-vitamins.

Specifically pertaining to fertility and IVF, Vitamin C has several proposed used, including the protection of oocytes from free radical cellular damage. There have been several studies looking at pregnancy outcomes when supplementing with oral Vitamin C at different stages of the IVF process. Two of these studies are highlighted below: 

Study 1: Ascorbic acid and infertility treatment (Crha 2003)

Methods: Prospective study in women treated with IVF and embryo transfers. Women in two IVF groups, 76 women (38 of them smokers, 38 non-smokers) were studied. Half the women (19 smokers and 19 non-smokers) were administered vitamin C in daily doses of 500 mg in so-called pellets allowing for gradual release over 8 to 12 hours. The control group consisted of the same number of smokers and non-smokers. Urine levels and follicle levels of Vitamin C were analyzed, as well as pregnancy rates.

Results: Ascorbic acid levels in follicles were significantly higher (p < 0.001) in women with vitamin C supplementation than in the control group (8.98 +/- 5.09 vs. 5.04 +/- 2.85 mg/l). The administration of vitamin C during the period of hormonal stimulation showed a statistically insignificant impact in terms of the higher number of pregnancies (34.2% vs. 23.7%). Vitamin supplementation had a greater impact on the number of pregnancies in the non-smokers' group (57.9% vs. 31.6%). The pregnancy rate was significantly higher (p < 0.01) in non-smoking women than in smokers--44.7% vs. 13.2%, which appears to be a reason for asking women to cease smoking prior to infertility treatment.

Conclusions:  Smoking appears to be very detrimental for IVF outcomes. Vitamin C appears to be helpful for increasing the number of pregnancies during IVF and embryo transfer.  

Study 2: Ascorbic acid supplement during luteal phase in IVF (Griesenger 2002)

Methods: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age <40 years, undergoing first IVF-embryo transfer cycles in two private outpatient infertility clinics. All women were stimulated by the same protocol. The mean age was 31.73 (+/- 4.4 SD) years.

Results: No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups.

Conclusions:  There was no clinical evidence of any beneficial effect, as defined by main outcome measures, of ascorbic acid on IVF-ET. Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment.

Our Take:

Vitamin C is an inexpensive and well tolerated supplement which can be easily incorporated into an IVF supplement routine. It appears taking as little as 500mg a day can improve the number of successful pregnancies for IVF. It seems to be of benefit during the follicular phase and the release of quality oocytes but does not appear to make a difference during the luteal phase, even in higher dosages. We would recommend taking 500mg twice daily, starting >90 days before starting IVF or trying to conceive.

Citations:

Florou, P., Anagnostis, P., Theocharis, P., Chourdakis, M., & Goulis, D. G. (2020). Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials. Journal of assisted reproduction and genetics, 37(10), 2377–2387. https://doi.org/10.1007/s10815-020-01906-3

Chu, J., Gallos, I., Tobias, A., Tan, B., Eapen, A., & Coomarasamy, A. (2018). Vitamin D and assisted reproductive treatment outcome: a systematic review and meta-analysis. Human reproduction (Oxford, England), 33(1), 65–80. https://doi.org/10.1093/humrep/dex326

Gorman, S., Zafirau, M. Z., Lim, E. M., Clarke, M. W., Dhamrait, G., Fleury, N., Walsh, J. P., Kaufmann, M., Jones, G., & Lucas, R. M. (2017). High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium. Journal of AOAC International, 100(5), 1337–1344. https://doi.org/10.5740/jaoacint.17-0087

Pilz, S., Zittermann, A., Obeid, R., Hahn, A., Pludowski, P., Trummer, C., Lerchbaum, E., Pérez-López, F. R., Karras, S. N., & März, W. (2018). The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data. International journal of environmental research and public health, 15(10), 2241. https://doi.org/10.3390/ijerph15102241

Espino, J., Macedo, M., Lozano, G., Ortiz, Á., Rodríguez, C., Rodríguez, A. B., & Bejarano, I. (2019). Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment. Antioxidants (Basel, Switzerland), 8(9), 338. https://doi.org/10.3390/antiox8090338

Qin, J. C., Fan, L., & Qin, A. P. (2017). The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis. Journal of gynecology obstetrics and human reproduction, 46(1), 1–7. https://doi.org/10.1016/j.jgyn.2016.01.002

Zheng, X., Lin, D., Zhang, Y., Lin, Y., Song, J., Li, S., & Sun, Y. (2017). Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine, 96(49), e8842. https://doi.org/10.1097/MD.0000000000008842

Regidor, P. A., Schindler, A. E., Lesoine, B., & Druckman, R. (2018). Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Hormone molecular biology and clinical investigation, 34(2), /j/hmbci.2018.34.issue-2/hmbci-2017-0067/hmbci-2017-0067.xml. https://doi.org/10.1515/hmbci-2017-0067

 Crha, I., Hrubá, D., Ventruba, P., Fiala, J., Totusek, J., & Visnová, H. (2003). Ascorbic acid and infertility treatment. Central European journal of public health, 11(2), 63–67.

Griesinger, G., Franke, K., Kinast, C., Kutzelnigg, A., Riedinger, S., Kulin, S., Kaali, S. G., & Feichtinger, W. (2002). Ascorbic acid supplement during luteal phase in IVF. Journal of assisted reproduction and genetics, 19(4), 164–168. https://doi.org/10.1023/a:1014837811353