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Women’s Health – Fertility

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Women’s Health – Fertility

Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

A
Systematic review or meta-analysis of human trials
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study

Women’s Health – Fertility

Infertility affects approximately 10 to 15% of couples.1 While the causes of infertility vary and can be linked both to male and female conditions, one contributing factor may be hormonal dysfunction in women.2

Testing levels of estrogen, progesterone, testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone can assist in identifying imbalances and addressing hormonal dysfunction in women. Hormone dysfunction may contribute to changes in ovulation rates or anovulation, and correcting levels of hormones may improve pregnancy success and reduce the probability of miscarriage.2,3,5

A number of factors may contribute to hormonal dysfunction, including environmental disturbances. Research suggests that endocrine disruptors, which may be present in air pollution, are correlated with increased rates of miscarriage, reduced live birth rates, and increased levels of nitrogen dioxide and ozone in populations undergoing in vitro fertilization (IVF).4

In addition, hormonal dysfunction is commonly seen in conditions such as polycystic ovarian syndrome (PCOS). Low serum vitamin D in women with PCOS appears to be correlated with endocrine disturbances.1 Addressing imbalances in hormones, such as androgens, testosterone, and dehydroepiandrosterone, may be beneficial in the treatment of PCOS.5

Improving the quality and maturation of oocytes also demonstrates promising results in women with or without PCOS undergoing ovulation induction.5,6,8

Based on current research findings, the ingredients in the protocol below have demonstrated efficacy in improving a variety of factors associated with improving female fertility.

Myo-inositol

Dosing: 2000-6000 mg with 100-400 mcg folic acid, twice per day, 2-3 months, or 4000 mg with 400 mcg folic acid, once per day, 3 months6,7,8,9,10

  • Poor responders undergoing intracytoplasmic sperm injection (ICSI) who received myo-inositol and folic acid supplementation experienced improved ovarian responses to gonadotropins, demonstrated by higher ovarian sensitivity index scores, as well as increased mature metaphase II oocytes rates and reduced total rec-FSH units compared to patients who received folic acid alone6
  • Supplementation of myo-inositol three months prior to follicular stimulation and in vitro insemination reduced the number of mature oocytes, improved total gonadotropin scores correlating with an increase in implantation rate, and subsequently reduced the total required dose of rFSH7
  • Myo-inositol supplementation decreased the number of immature oocytes and increased the number of oocytes recovered, embryos transferred, and follicular size to more than 15 mm at the time of ultrasound8
  • Myo-inositol or D-chiro-inositol supplementation increased the frequency of menstrual cycles and improved ovulation rate with or without metformin administration5
  • Myo-inositol improves sensitivity to clomiphene citrate, demonstrated by increased ovulation rates from 42% to 65.5% and pregnancy rates from 42.4% to 53.8% when compared to historical cohort9
  • Infertile PCOS patients undergoing intrauterine insemination (IUI) who received myo-inositol prior to controlled ovulation induction (COH) experienced less cancelled cycles and increased rates of pregnancy and number of spontaneous pregnancies, resulting in lower rFSH dose requirements and duration of ovulation induction10
Myo-inositol in the Fullscript catalog

Vitamin D3

Dosing: 50,000 IU, administered once, or 1000 IU per day, 6 months11,12

  • Repletion of vitamin D increases clinical pregnancy rates, the likelihood of positive pregnancy tests, and live birth rates in vitamin D-deficient individuals undergoing assisted reproductive technology (ART) when compared to a control group13
  • Anti-Müllerian hormone (AMH) is regulated by vitamin D serum levels, demonstrated by a decrease in AMH after supplementation in PCOS patients and an increase in AMH after supplementation in healthy ovulatory women11,12,14
  • Vitamin D3 led to improvements in menstrual cycle frequency in vitamin D-deficient women with PCOS1
Vitamin D3 in the Fullscript catalog

Prenatal multivitamin

Dosing: Prenatal formulation including 800 mcg folic acid, 28 days prior to conception and continued through the second missed menstrual period, or prenatal formulation including 800 mcg folic acid, 4-6 weeks prior to ovulation induction15,16

  • Supplementation of multivitamin for 28 days prior to conception and though the second missed menstrual period positively increased fertility from 2.7% to 3.8%, measured by cumulative conceptions and multiple births, and reduced neural tube defects in women with or without ovarian stimulation15
  • Subfertile women treated with clomiphene citrate and gonadotropins undergoing ovulation induction experienced higher pregnancy rates (66.7%) and required fewer pregnancy attempts with concomitant multiple micronutrient supplementation compared to folic acid alone (39.3%)16
  • Micronutrient supplementation improved pregnancy rates and live birth rates when administered during in-vitro fertilization (IVF) therapy17
Prenatal multivitamin in the Fullscript catalog

N-acetylcysteine (NAC)

Dosing: 1200 mg, starting on day 3 of the cycle for 5 days, 12-24 consecutive cycles;
or 1800 mg in patients with PCOS, once per day, 8-12 weeks18,19,20,21

  • NAC administered concomitantly in clomiphene citrate-resistant PCOS patients increased ovulation and pregnancy rates18
  • When comparing clomiphene citrate treatment alone to concomitant treatment with NAC or metformin in PCOS patients, the group receiving NAC experienced higher rates of pregnancy (20% compared to 10% in the clomiphene citrate and clomiphene citrate/metformin groups), improved ovulation and peak endometrial thickness, and an increased number of ovulatory follicles larger than 18 mm19,22
  • NAC administered with unilateral laparoscopic ovarian drilling (LOD) in clomiphene citrate-resistant PCOS patients increased ovulation rates from 67% to 87% and pregnancy rates from 57% to 77%, lowered miscarriage rates from 23.5% to 8.7%, and subsequently resulted in live birth rates of 67% compared to 40% in the placebo group20
NAC in the Fullscript catalog

Ashwagandha (Withania somnifera)

Dosing: 300 mg KSM-66 extract, twice per day, 8 weeks23,24

  • Ashwagandha supplementation enhanced sexual behavior in females, measured using the female sexual function index (FSFI) and female sexual distress index (FSDI)25
  • Supplementation improved FSFI and FSDS scores, and increased number of sexual encounters23
  • Ashwagandha supplementation improved sexual function, demonstrated by an increase in FSFI score by 122.67%, a total score accounting for improvements in arousal (62.09%), lubrication (59.30%), orgasm (82.05%), and satisfaction (62.33%) when compared to baseline24
Withania somnifera in the Fullscript catalog

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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References

1
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/22275473/
4
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/30594197/
5
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/28544572/
13
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/29149263/
14
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/32481491/
17
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/28919239/
25
Systematic review or meta-analysis of human trials
a
https://pubmed.ncbi.nlm.nih.gov/29670898/

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