Key Integrative Interventions & Clinical Evidence For Unexplained Infertility and Supplementation

We cannot stress enough: customization is key to success and outcomes. Simply researching best supplements will not usually result in positive fertility outcomes, and if they do, that is extremely lucky. One must be highly educated, assess the entire picture, and create a very individualized plan. That being said, a lot of interesting studies are finally coming out helping people become more fertile. 

What are the best supplements for fertility? 

1. Coenzyme Q10 (CoQ10 / Ubiquinol)

  • Clinical Focus: Mitochondrial energy production and oocyte quality.

  • Evidence Summary: Age-related decline, particularly in women over 35 years old, in oocyte quality is heavily linked to mitochondrial dysfunction and reduced cellular ATP production. Thankfully we have a supplement that can address this and even IVF centers are now following our recommendations about incorporating CoQ10 into your daily vitamin regimen. CoQ10 supplementation improves mitochondrial function, oocyte quality (think egg quality), and ovarian reserve. These cumulative aspects support higher clinical pregnancy rates and improve the quality of embryos specifically in women with diminished ovarian reserve DOR. 

Coenzyme Q10 (CoQ10)  Dosing

  • Target Dosing: 200 mg to 600 mg daily in divided doses (we strongly suggest Ubiquinol for improved bioavailability) for at minimum of  8 to 12 weeks prior to conception or IVF or ART cycles.  

2. DHEA (Dehydroepiandrosterone)

  • Clinical Focus: Follicular androgen microenvironment and a woman’s ovarian responsiveness.

  • Evidence Summary: This is easily tested through a blood test. We often test this especially in women over 35 or women who already have perimenopausal symptoms or have had multiple failed IUI and IVF cycles. DHEA acts as a precursor for follicular steroidogenesis in a woman’s body. Proper dosing and supplementation helps optimize intraovarian androgen levels, promoting recruitment of pre-antral follicles. This ultimately improves a woman’s ovarian response while undergoing fertility treatments and even in naturally conceived cycles. 

  • Evidence-Based Dosing: 25 mg to 75 mg daily for 12 weeks 

We choose the best dose based on age, failed ART cycles, and blood levels. 

  • Clinical Note: We always suggest evidence based medicine and in our functional medicine we test our patients. Serum DHEA-S and total testosterone levels should be monitored prior to and during therapy.

3. Melatonin

  • Clinical Focus: Intrafollicular potent antioxidant protection and oocyte maturation in women.

  • Evidence Summary: Studies have found higher concentrations of melatonin in follicular fluid protect oocytes from ROS-induced damage. Again, we test this in our practice to make an informed decision for our patients and their personalized supplementation suggestions. Supplementation is often associated with higher fertilization rates, an increased proportion of mature (MII) oocytes, and higher top-quality embryo numbers. This benefits patients trying naturally too. For most, it also helps them obtain sound sleep.  

  • Target Dosing: 3 mg daily taken at night prior to bedtime  but dosing varies on patient response and sensitivity. 

4. Vitamin D3

  • Clinical Focus: Lower miscarriage rates, healthier hormone balance, Anti-Müllerian hormone (AMH) modulation, endometrial receptivity, and improved implantation rates.

  • Evidence Summary: Receptors for Vitamin D are widely expressed in reproductive tissues throughout a woman’s body. Increasing hypovitaminosis D, often helps with energy in low energy patients, supports follicular maturation and endometrial receptivity. Several clinical studies prove significantly higher implantation rates when combined with basic antioxidant regimens. We customize our recommendations and test often for optimal levels and best results. 

  • Evidence-Based Dosing: 2,000 IU to 4,285 IU daily . This would equate up to 30,000 IU weekly. However, we suggest daily dosing,  titrated to maintain optimal serum 25(OH)D levels (typically 40–60 ng/mL). We test this in our functional medicine practice for the best outcomes and results in our patients. 

5. Inositol also known as Myo-inositol

  • Clinical Focus: Insulin sensitivity and follicular signaling during a woman’s cycle and ovulation.

  • Evidence Summary: Inositol supports metabolic health and oocyte development 

    • Effect Level: Small Improvement however, in clinic we see patients who feel better, their acne resolves and their LH monitoring improves. This can also help metabolically which is really helpful for women with PMOS (formerly known as PCOS) with their weight management. 

  • Evidence-Based Dosing: 2,000 mg once or twice daily with observing bowel tolerance and weight discrepancy. 

6. NAD+ Precursors (NMN / NR)

  • Clinical Focus: Cellular repair, sirtuin activation, and oocyte spindle integrity.

  • Evidence Summary: Nicotinamide Mononucleotide (NMN) supplementation helps restores systemic and cellular NAD+ levels in women. 

  • Studies have shown that supplementation with multiple micronutrients (MMN), including antioxidants, positively influences clinical fertility outcomes. Improving fertilization rates, positive pregnancy numbers, and most importantly, live birth rates in patients undergoing fertility treatments like in-vitro fertilization (IVF) and ovulation induction (OI) with intercourse or IUI. (Skoracka 2021)(Alrashidi 2024)

  • Evidence Grade: B (Moderate potential)

  • Effect Level: Small Improvement We cautiously recommend these supplements and look forward to more clinical evidence to prove their efficacy. 

Lifestyle Suggestions to Optimize Fertility

How can I improve my fertility at home? 

Lifestyle modifications serve as foundational, at-home support to optimize reproductive endocrinology and endometrial health and healthy pregnancy. 

You are what you eat. 

  • Nutrition: Always prioritize real food, veggie forward, nutrient-dense mediterranean-style dietary pattern rich in anti-inflammatory fats that include omega-3s. Look for super bright colored antioxidants; eat your rainbow daily is a good place to start. Add this with high-quality proteins to support cellular membrane integrity and reduce systemic inflammation by avoiding farmed fish. Choose soups over smoothies every time. 

Is sleep really that important for my hormones: 

  • Sleep & Circadian Alignment: You bet it is. Try to get 7–9 hours of continuous, uninterrupted sleep. Choose  a fully dark room with blackout shades or an eye shade to maintain natural nocturnal melatonin secretion and circadian hormone regulation. Consider moving pets out of your room. If you don’t feel rested after 9 hours of continuous sleep, a sleep study to rule out sleep apnea may be warranted. But listen to your body, some people just require more sleep than others. If ten hours is your sweet spot, honor that and get those zzz’s. If you have trouble sleeping seek out acupuncture to help you go deep and stay deep. 

  • Stress Management: Acupuncture is the number one treatment for stress. If literally help reset your nervous system, gets you out of fight or flight and all you have to do is lie there. Implement intentional daily stress-reduction practices including: mindfulness, acupuncture, yoga or zen walking  to regulate HPA axis activity and reduce cortisol-induced disruption of gonadotropin signaling. 

  • Exercise, Sex for Fun and Movement: Exercise is critical to your health and hormones. Chose mild to moderate-intensity daily activity to support pelvic blood flow and insulin sensitivity. Be sure to avoid extreme physical overexertion (think hit workouts, triathlons, marathons, heavy intense weight lifting)  that could compromise luteal phase function, excrete excess cortisol and keep your body stress, not relaxed. Make sex fun again. Don’t always engage when you are fertile. Don’t like exercise at all? Find something fun, like paddling or fun dance classes, or even hula hoop classes. If you are moving, you are grooving and that counts. 

Lifestyle modifications should be considered first-line interventions for supporting women’s hormones and a healthy reproductive system. Diet, exercise, stress, and sleep directly and positively impact female fertility. (Zhao 2018)(Vitale 2017) . Prioritizing these things you have control over,  helps promote not just your health but also imparts a positive impact on you and your partners reproductive health. 

  • Studies have shown that supplementation with multiple micronutrients (MMN), including antioxidants, positively influences clinical outcomes such as fertilization rates, pregnancy rates, and live birth rates in patients undergoing fertility treatments like in-vitro fertilization (IVF) and ovulation induction (OI). (Skoracka 2021)(Alrashidi 2024)

If you try these methods, but still have no luck, you may want to consider seeing a professional acupuncturist or fertility expert. Dealing with infertility can get harder as time progresses since it can be more stressful and frustrating, so getting the support and help of a medical professional can help ease the pressure, and have you on your way to a healthy, happy, pregnancy. Please reach out anytime. We are here to help.

Colin Eggleston