Condition Monograph: Unexplained Female Infertility

Definition of Condition

Female infertility is defined as the “inability to conceive a child after 12 months of regular unprotected intercourse (at least twice weekly) with the same male partner and in the absence of male causes (Pizzorno & Murray, 2013).” About 80% of infertility cases can be related to specific causes such as endometriosis or polycystic ovary syndrome (PCOS); however, the other 20% remained unexplained by traditional Western medicine (Reid, 2015). Unexplained infertility is defined as the failure to conceive after 12 months of trying, with normal semen samples and no other abnormalities found (Shahin et al., 2008). 

Body Systems Affected 

The female reproductive system.

Pathophysiology

Infertility is believed to affect 1 in 7 couples in the United States (Pizzorno & Murray, 2013). A person’s fertility may be a reflection of his or her general health and wellbeing, however age is one of the greatest risk factors for female infertility. As a woman ages, the reproductive system ages as well, resulting in the decreased quantity and quality of follicles preserved in the ovaries. As the number of oocytes decline, a woman’s menstrual cycle shortens and fertility decreases (Sharma et al., 2013). In addition to preventing the natural conception of a child, infertility can also cause anxiety, depression, and other forms of psychological distress. 

Allopathic Diagnosis and Treatment

Symptoms

The inability to conceive a child after 12 months of regular unprotected intercourse in the absence of male causes. 

Diagnosis

When male factors are ruled out as potential causes, and there are no other female reproductive abnormalities found, then a woman may have unexplained infertility after at least 12 months of attempting pregnancy. For women over 35 years of age, infertility may be diagnosed after only 6 months. Standard infertility evaluation includes: semen analysis, assessment of ovulation, a hysterosalpingogram, and tests for ovarian reserve and laparoscopy. When the results of this evaluation is normal, practitioners assign a diagnosis of unexplained infertility (Quaas & Dokras, 2008).

Treatment

Assisted reproductive technology (ART) is a common treatment for infertility. The treatment handles both a woman’s egg and a man’s sperm, and works by removing eggs from a woman’s body, injecting sperm to make embryos, and returning the fertilized eggs to the woman’s body (Medline Plus, n.d.). In vitro fertilization (IVF) is the most common and effective type of ART. IVF has one of the highest success rates for therapeutic options for infertile couples, however it can be expensive and involve a long preparation time (Djaali et al., 2019). Alternative therapies may bypass the risks of IVF, which include psychological stress, operative risks, multiple gestations, and ovarian hyperstimulation syndrome (OHSS) (Shahin et al., 2008). Prior to an IVF cycle, couples should consider a 3 to 4 month preconception program for detoxification and nutritional purposes, optimizing the chances for success (Pizzorno & Murray, 2013). Dietary and lifestyle recommendations may be encouraged, however all possible interactions with IVF medications must be considered. 

Other treatments for unexplained fertility include: expectant observation with timed intercourse and lifestyle changes, intrauterine insemination (IUI), and controlled ovarian hyperstimulation (COH) with IUI (Quaas & Dokras, 2008). IUI involves the placement of washed sperm into the uterine cavity around the time of ovulation. Both clomiphene citrate and gonadotropins have been used for COH, in combination with IUI or alone. Lifestyle modifications to improve fertility are outlined below. 

Complications

IVF can cause side effects in some women. Fertility medications can cause nausea, stomach pains, headaches, and hot flushes (Infertility, 2016). OHSS is a rare complication of IVF and occurs when too many eggs develop in the ovaries, causing them to become large and painful. There is also a risk of an ectopic pregnancy with IVF, which occurs when the embryo implants in the fallopian tubes rather than in the womb. Fertility treatment also increases the risk of having multiple pregnancies (In Vitro Fertilization, n.d.). Additional risks to having multiple pregnancies include premature delivery and low birth weight. IVF also involves a significant financial commitment, as the treatment is often not covered by insurance plans and a single IVF treatment can range from $12,000-$17,000. Finally, fertility treatments can cause a great deal of psychological stress, affecting a woman’s quality of life and causing anxiety and/or depression. 

When to Refer

A woman should always consult her primary care physician first about trying to conceive, especially if she has been trying without success for over 12 months (or 6 months if over 35 years of age). If considering herbal supplements, she should also ensure that they do not conflict with any other medications being taken. In particular, a patient should consult her primary care physician about using any complementary and alternative medicine (CAM) treatments if undergoing ART, as some alternative therapies could interact with ART (O’Reilly et al., 2014). Finally, patients diagnosed with unexplained infertility are at particular risk for depression and anxiety due to the diagnosis, and should be referred to a trained psychotherapist if needed.

Integrative Perspective of Causes

There are several possible risk factors for female unexplained infertility. Age is the greatest modifiable risk factor; the probability of conception declines steadily after age 31, with a more rapid decline after age 35 (Pizzorno & Murray, 2013). Also, as a woman ages, the risk of having a child with Down syndrome and total chromosomal abnormalities increases significantly. Body mass index (BMI) and body fat percentage are other important risk factors. A woman should ensure that her body fat percentage is between 20% and 25% to support fertility. BMI should range between 20 and 24 for optimum fertility (Chavarro et al., 2008). Exposure to environmental pollutants can also negatively impact fertility and can be found in some makeup, fragrances, hair dyes, nail polish, and other beauty products (Pizzorno & Murray, 2013). Smoking, alcohol consumption, and caffeine intake have also been found to impair female fertility. Finally, stress, anxiety, and depression are risk factors for female infertility; women who take measures to reduce anxiety and depression may increase their chances of conception (Sharma et al., 2013). 

Specialized Integrative Analysis

There are several methods to assess ovulation including: basal body temperature (BBT) recordings, urinary luteinizing hormone (LH) ovulation predictor kits, and mid luteal serum progesterone testing (Quaas & Dokras, 2008). BBT recordings can be inexpensive, yet are also difficult to interpret and can be frustrating for the patient. Ovulation predictor kits can be used to appropriately time intercourse and are useful for women with relatively short menstrual cycles. Mid luteal progesterone levels are generally measured around day 21 for women with regular (28 day) cycles. For women with irregular menses, it is best to use an ovulation kit to measure progesterone levels 7 to 8 days after the LH surge is detected. Progesterone levels higher than 3 ng/mL suggest that ovulation has occurred and levels higher than 10 ng/mL are optimum. 

Integrative support Protocols

Lifestyle Modifications

Smoking, caffeine, and alcohol. Smoking is one of the most readily avoidable causes of infertility (Pizzorno & Murray, 2013). In women, smoking has been found to increase the thickness of the zona pellucida, the membrane that forms around an ovum, making it difficult for sperm to penetrate it. Caffeine should be limited to no more than 2 cups a day, and alcohol should be reduced to no more than four standardized drinks per week (Quaas & Dokras, 2008). 

Stress. Stress can alter levels of follicle stimulating hormone and LH, which directly affect the synthesis of estrogen and progesterone and control ovulation in women (Chasse, 2013). Infertility diagnosis and treatments may cause a great deal of stress for couples, creating a negative cycle that makes it even more difficult to conceive. Women who have participated in a cognitive behavior intervention or a support group have been found to have higher conception rates (Sharma et al., 2013).

Nutrition. The Mediterranean diet has been found in many studies to benefit female fertility. It was found to improve the number of available embryos in the IVF cycle of infertile women (Sun et al., 2019). When compared with an overall healthy and low-processed diet, the Mediterranean diet was found to increase the chance of pregnancy after IVF and Intracytoplasmic Sperm Injection (ICSI) treatment by about 40%, despite considerable similarities between the diets (Vujkovic et al., 2010). This could be due to an increased intake of omega-6 fatty acids from vegetable oils, or an increase in vitamin B6 levels, which may increase reproductive function. Adherence to the Mediterranean diet has also been linked to lower adiposity and obesity risk, possibly due to the high consumption of satiating dietary fiber and the low degree of energy density in the diet (Boghossian et al., 2013). However, the Mediterranean diet is not the only dietary pattern that will improve female fertility. General dietary guidelines are as follows: an abundant intake of fruits, vegetables, legumes, whole grains, and nuts; high-to-moderate intake of vegetable oils and fish; low-to-moderate intake of eggs, dairy products, and poultry; low intake of red meat, sugar, and sweetened beverages; and avoid trans fatty acids as much as possible. 

Physical exercise. Moderate and regular exercise has been found to benefit female fertility; however, excessive exercise can negatively alter energy balance and affect the reproductive system (Sharma et al., 2013). One must ensure that energy demand is not exceeding dietary energy intake. Extreme exercise can also lead to anovulation, whereas moderate exercise may decrease the risk of infertility in women (Collins & Rossi, 2015). The exact amount of exercise that will improve the fertility of each individual must be assessed on a case-by-case basis.

Acupuncture. Acupuncture is increasingly used as an adjunctive therapy to ART. Acupuncture has been found to increase the chances of successful IVF through several possible mechanisms: by modulating neuroendocrine factors, increasing blood flow to the uterus and ovaries, modulating immune factors, and/or reducing stress and depression (Djaali et al., 2019). In a randomized controlled trial, sub/infertile women were offered an intervention of acupuncture and lifestyle modification or lifestyle modification only (Cochrane et al., 2016). The study found that the acupuncture intervention, compared to lifestyle only, resulted in significant increases in fertility awareness and quality of life measures in relation to wellbeing. Acupuncture was found to shorten the time to conception by half. Another study by Yun et al. (2019) found that acupuncture may improve fertility parameters for women not undergoing ART. In this systematic review and meta-analysis of 22 randomized controlled trials with 2,591 participants, significant improvement was observed in pregnancy rate, LH levels, and endometrial thickness compared to controls. 

Multiple-micronutrient supplementation. Restoring micronutrient levels to recommended levels could beneficially affect the mechanisms involved in fertility (Schaefer & Nock, 2019). This may improve oocyte and embryo quality, reduce the time to conception, and increase a woman’s chances of becoming pregnant.

Herbal Protocols 

Cimicafuga racemosa (Black Cohosh). C. racemosa was traditionally used by Native Americans to alleviate general gynecological symptoms, as well as joint pain and muscle aches (Rowland et al., 2007). The beneficial effects are presumably from phytoestrogens, which alleviate gynecological problems related to estrogen deficiency by increasing estradiol levels. In modern application, C. racemosa is primarily used for treating menopausal symptoms and regulating estrogen levels during this life stage (Pizzorno & Murray, 2013). However, it also has potential for improving female fertility. In a study on C. racemosa and women with unexplained fertility, Shahin et al. (2008) found that C. racemosa supplementation resulted in greater pregnancy rates when used with clomiphene (an ovulatory stimulant medication) than the control group that used clomiphene alone. C. racemosa rhizome dry extract was given at a dose of 120 mg per day, on days 1 to 12 of the menstrual cycle, in addition to 150 mg clomiphene citrate per day on days 3 to 7. C. racemosa can increase the risk of miscarriage and should be avoided during pregnancy (Natural Medicine Database (NMD) Black Cohosh, 2019). Typical dosage of fluid extract is 2-4 mL (0.5 to 1 tsp) three times daily.

Angelica sinensis (Dong Quai). A. sinensis is used in traditional Chinese medicine to nourish the blood, restore the body’s natural balance, and serve as a female tonic for a variety of gynecological conditions (Pizzorno & Murray, 2013). It may function as a relaxing blood mover that can improve circulation to the uterus, thereby supporting implantation. It may also increase sexual desire and help to regulate the reproductive cycle (Rowland et al., 2007). A. sinensis has uterine stimulant and relaxant effects that could theoretically adversely affect pregnancy and should not be taken while pregnant (NMD Dong Quai, 2019). Typical dosage of fluid extract is 2-4 mL (0.5 to 1 tsp) three times daily. 

Tribulus terrestris (Tribulus). T. terrestris is used in herbal medicine for female reproductive disorders, including infertility (Pizzorno & Murray, 2013). It is believed to have FSH-stimulating properties that help to initiate ovulation and improve conception rates when administered at the start of the menstrual cycle. T. terrestris helps to increase cervical fluid, which substantially supports conception. Patients notice an immediate increase in libido and cervical fluid release, which promotes confidence in their natural fertility. A study by Gama et al. (2014) found that administration of T. terrestris enhanced female sexual function and increased dehydroepiandrosterone (DHEA) levels, suggesting clinical improvement of female sexual dysfunction with treatment. In this study, 1 tablet of 250 mg was given three times a day for 90 days.

Vitex agnus-castus (Chaste Berry). V. agnus-castus is believed to benefit anovulatory and menstrual cycles (Pizzorno & Murray, 2013). It has been found to improve hormone levels and pregnancy outcomes in subfertile women. In a study of 93 women struggling to conceive, an herbal formulation called Fertility Blend (of which V. agnus-castus was the main component) was found to significantly improve fertility parameters compared to placebo (Niroumand et al., 2018). In women who were infertile due to progesterone deficiency, 30 drops twice daily for at least 3 months has been used to increase the chance of pregnancy (NMD Vitex agnus-castus, 2019). The usual dosage of V. agnus-castus in tablet or capsule form is 175-225 mg per day. As liquid extract, typical dosage is 2-4 mL (0.5-1 tsp) per day.

References

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Chasse, J. (2013). Integrative approaches to infertility for women. Townsend Letter. Retrieved from: https://web.a.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=3&sid=0662a3bd-23fc-4ed0-8f15-61f9469608f6%40sdc-v-sessmgr03

Chavarro, J.E., Willett, W.C., & Skerrett, J.E. (2008). The fertility diet: Groundbreaking research reveals natural ways to boost ovulation & improve your chances of getting pregnant [Kindle version]. Retrieved from Amazon.com.

Cochrane, S., Smith, C.A., Possamai-Inesedy, A., & Bensoussan, A. (2016). Prior to conception: The role of an acupuncture protocol in improving women’s reproductive functioning assessed by a pilot pragmatic randomised controlled trial. Hindawi Publishing Corporation. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868913/

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