Fertility Challenges

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CHAPTER 12 Fertility Challenges

Infertility is defined as the inability to conceive after 12 months of unprotected intercourse in a couple of reproductive age attempting to conceive. Approximately 90% of couples achieve conception within this time, and a further 15% of normally fertile couples take longer than 12 months to become pregnant. Research has shown that even couples in their late thirties have a 91% chance of conceiving naturally within 2 years, and recent studies estimate that an average of 25% to 40% of women have a live birth without treatment during the 3 years after the first infertility consultation, even without treatment. 1 2 3 Nevertheless, of the approximately 60 million women of reproductive age in the United States in 1995, about 1.2 million, or 2%, had had an infertility-related medical appointment within the previous year and an additional 13% had received infertility services at some time in their lives.⁴ This number has increased in recent decades because of societal demographic changes, particularly the aging of the baby boom generation, leading to an increased size of the reproductive age population, and more couples delaying fertility for the sake of careers.¹

Infertility is not synonymous with sterility and it is important to differentiate these terms. Sterility is defined the inability to achieve pregnancy and affects only 1% to 2% of couples.² Primary infertility refers to those who have never before conceived and secondary infertility to those who have achieved conception some time in the past (regardless of pregnancy outcome) and thereafter became infertile.⁵

FEMALE FACTORS AFFECTING FERTILITY

The main types of female infertility include ovulatory disorders (25%) and tubal disease (20% to 25%), including endometriosis (10%). Ovulatory factors are suspected when menstrual abnormalities are reported. Male infertility is the primary cause in approximately 25% of cases and contributes to an additional 15% to 25% of cases. Infertility results from unexplained causes in up to 20% of cases.¹ Thorough evaluation of the couple will point to a probable cause in 85% to 90% of cases.² Ovarian factors are primarily associated with follicular phase disruptions. An inadequate luteal phase is said to account for only 3% to 4% of fertility failure. Examples of all of the factors that account for fertility challenges are listed in Table 12-1.

TABLE 12-1 Causes of Fertility Challenges

FACTOR	EXAMPLES
Ovulatory	Defects of the ovaries Anovulatory cycles Hyperprolactinemia Hypothalamic dysfunction Pituitary dysfunction Gonadal dysgenesis Premature ovarian failure Ovarian resistance

Metabolic

Androgen excess (adrenal or neoplastic causes)

Pelvic

Common infection (genitourinary infections such as Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Neisseria gonorrhoeae causing inflammation, infections and scar tissue)

Chronic inflammation manifesting as pelvic inflammatory disease (PID)

Uterine or fallopian adhesions

Endometriosis (attributed to 5% of cases of infertility)

Fibroids

Structural abnormalities

Cervical (evident in only about 3% of cases)

Factors are and can include:

Hostile mucus (sperm antibodies, abnormal viscosity or pH)

Cervicitis and infections

Acquired surgical damage to the mucus producing endocervical glands (cone biopsy, laser ablation, cryotherapy) associated with cervical dysplasia or neoplasia

Immune-mediated

Lack of blocking antibodies

Autoimmune disease such as SLE

Immunophenotypes

Anti-thyroid antibodies

Antiphospholipid syndrome (APS)

Data from Kaider A, Kaider B, Janowicz P, et al.: Immunodiagnostic evaluation in women with reproductive failure, Am J Reprod Immunol 42(6):335-346, 1999.

Unexplained and coexisting factors account for approximately 10% of infertility cases and can be a result of environmental and/or occupational exposure to toxicity such as heavy metals, radiation, solvents, DES, smoking, and exogenous androgens and/or estrogens from environmental and food sources. Nutritional deficiency, stress, and age can all contribute to fertility problems. Abnormal body mass index (BMI), including being underweight or overweight, can cause amenorrhea and infertility. The fertility of a woman begins to significantly decline between the ages of 35 to 38 and sharply declines after the age of 40.

DIAGNOSIS

Initial evaluation of infertility must include a thorough workup of both partners for male and female factors that might cause fertility problems.

Noninvasive Home Evaluation and Patient Participation: Thermo-Symptal Monitoring and Mucus and Cervical Evaluation for Detection of Ovulation

As fertility evaluation can be physically invasive, traumatic, and cost prohibitive, there are some useful tests women can do themselves at home. One easy technique is Thermo-Symptal monitoring, which involves the monitoring and recording of the basal body temperature (BBT) and recording of cervical mucus secretions on a daily basis throughout the cycle. Although convenient and cost-effective, Thermo-Symptal monitoring requires consistent commitment and a learned awareness of the body’s subtle signs of fertility. This awareness can help the couple refine conception timing and allow the woman sense of participation in her own program toward achieving pregnancy.

Basal Body Temperature Monitoring

The luteal phase of the cycle is characterized by the production of progesterone from the corpus luteum. Progesterone is a thermogenic hormone elevating the core body temperature in the luteal phase of the cycle. When adequate progesterone is produced as a result of ovulation having occurred, the BBT elevates and remains elevated for approximately 10 days after ovulation, until either menses occurs, in which the temperature will drop, or pregnancy is established, in which the temperature will continue to elevate to a third phase as the progesterone continues to be produced into the pregnancy. This elevation in temperature usually occurs 1 to 2 days after ovulation.

Interpretation of the Basal Body Temperature

In the follicular, preovulatory phase of the menstrual cycle in a healthy woman, the temperature reading is approximately 97°F. An increase in temperature greater than 97°F in the luteal phase, after day 13 or 14, is indicative of a normal ovulation in 90% of cases. If the temperature maintains above this temperature after 16 days, this is suggestive of pregnancy. The BBT is measured orally first thing upon waking in the morning, before any activity, with a specific fertility thermometer (thermocrystal basal thermometer). The temperature is best taken at the same time each day, after at least 6 hours of sleep. The routine should commence on the first day of her cycle, which corresponds to the first day of menstrual flow. Sleeping with an electric blanket, heated waterbeds, or other heating or cooling devices near the body may disrupt the BBT and adversely affect the reading; hence, they need to be avoided while monitoring BBT. BBT cannot be used by the couple to predict ovulation; it only confirms ovulation retrospectively by indicating the event of luteinization but is considered a relatively reliable assessment of the preovulatory phase. Therefore, used as a single tool, it proves to be of limited value. When BBT is monitored concurrently with cervical mucus observations, it can be a very informative and valuable tool for the couple.

Monitoring Cervical Mucus Changes

Daily monitoring of the texture, quality, and quantity of cervical mucus secretions can be useful to predict ovulation. Cervical mucus secretions change throughout the cycle under the influence of estrogen and progesterone. Approximately 2 or 3 days before ovulation occurs, the estrogen levels peak and the nature of the mucus changes from a pasty thick or milky consistency to a distinctive “spinnbarkeit”: stretchy mucus (usually 6 to 10 cm) of wet consistency and opaque color. It resembles a similar texture and nature to raw egg white. At this stage of the cycle, the mucus is an optimal reservoir to nourish sperm and encourage their survival for conception. When seen under a microscope, fertile spinnbarkeit mucus dries into a distinctive crystalline fernlike pattern. Small, inexpensive ovulation predictor microscopes for home use are available to assist couples in predicting ovulation. Saliva is usually used on the microscope as an alternative to cervical mucus, because saliva mimics the ferning pattern of the spinnbarkeit at the ovulation time. When estrogen levels are lower in the early follicular phase and midluteal phase of the cycle, the mucus secretions are thin, milky, and sparse in nature. When a woman is monitoring cervical mucus, it is recommended she feel the texture of the mucus (at the vaginal opening) between the forefinger and thumb and not use toilet tissue to collect the sample. It absorbs moisture and may lead to misinterpretation of the mucus viscosity. Home test kits that measure urinary LH levels are available for ovulation prediction. These are single use tests and their disadvantage is the expense when used regularly.

The Texture and Shape of the Cervix

Some women experiencing infertility may produce inadequate quantities of cervical mucus or experience difficulty feeling the texture of the mucus. In this case, she can be taught to feel the texture of the cervix itself. When cervical tissue is not under the influence of peak estrogen levels it feels hard, cartilaginous (imagine feeling the end of the nose; this is a similar texture), and the cervical os is closed. At the time of the LH surge and estrogen peak, the cervix becomes soft, “ripe,” and palpable (imagine feeling the texture of the cheeks; this is a similar texture) and the cervical os is slightly open.

CONVENTIONAL TREATMENT APPROACHES

Despite developments in fertility knowledge and technologies, the overall prognosis for achieving childbirth with reproductive technologies is approximately 50%, and declines as women age. Each treatment option has overt and hidden costs, including emotional, physical, and financial burdens, often without justification because of lack of success. Couples entering fertility treatment need to be fully cognizant of the potential price of treatment in all of these areas, and the benefit vs. costs must be evaluated. Patients must also consider the high frequency and implications of a multiple pregnancy, a common outcome with assisted reproductive technologies. Psychological support should be available to all couples considering reproductive technologies, with no blame laid upon either partner, and a realistic appraisal of the chances for success and failure of treatment honestly provided. Reproductive expert Marcelle Cedars advises, “The option of child-free living should also be included in any discussion. At times couples must be advised to stop treatment if the likelihood for success is quite low. Frequently this is a very difficult time for both the patient and the physician, but fruitless treatment should be avoided.”¹

Ovulatory Factors

The conventional treatment of ovulatory factors is determined by the conclusive diagnosis made after clinical investigation. With conventional infertility therapy, the chances of conception are said to be 15% to 25% per cycle, depending on the degree of drug-induced ovarian stimulation. If failure to conceive after a maximum of 12 cycles persists, then assisted reproductive technology (ART) is recommended as the next option by allopathic medical reproductive specialists.

Ovarian Stimulation Therapy

Induction of ovulation is said to be successful in 90% to 95% of cases with administration of particular pharmaceutical drugs in a given scenario. Each given scenario depends on a specific set of circumstances, such as hormonal imbalances or failure of a prior drug approach.

In cases of elevated FSH, indicating ovarian failure, postmenopause or ovarian resistance, fertility cannot be restored using drugs. Options for these women include adoption, or embryo or egg donation. Success of pregnancy with embryo or egg donation is reported to be approximately 40%, but this does not reflect live birth statistics for the given scenario. This scenario also gives rise to multifactorial ethical, legal, financial, and psychosocial issues. In the case of chronic anovulation with normal FSH and normal prolactin levels, first line therapy is Clomiphene citrate, a nonsteroidal, antiestrogen drug. This drug is prescribed for women with oligomenorrhea, amenorrhea (including polycystic ovarian syndrome and psychogenic amenorrhea), and women who have sufficient estradiol levels or luteal phase deficiency (progesterone failure). This is administered orally at 50 to 250 mg daily orally on days 5 to 10 of the cycle. It is often combined with corticosteroids, estrogen, and midcycle human chorionic gonadotrophin (hcG) and followed up with monthly hormonal testing or ultrasound to establish the drug’s efficacy in stimulating the follicle and ovulation. Clomiphene citrate is reported to be successful in stimulating ovulation in 70% of cases. The pregnancy rate from use of this drug is only 35%. In 50% of women who use Clomiphene citrate, it stimulates more than one follicle, and the incidence of multiple births is 8%. It is recommended that it not be used for longer than six cycles. Use for longer than 12 months may increase the risk of ovarian cancer. Side effects of Clomiphene citrate include hot flashes, breast tenderness, mood swings, visual problems, thick cervical mucus, luteal phase deficiency (although it is routinely prescribed for this problem), ovarian enlargement, abdominal-pelvis bloating, and discomfort. Ovarian hyperstimulation syndrome has been associated with this drug therapy.

Where there is failure to respond to Clomiphene citrate, or in patients with pituitary insufficiency and/or hypothalamic insufficiency, unexplained infertility, or endometriosis, a second line of treatment is used to induce ovarian stimulation: human menopausal gonadotropin (hMG), a pituitary peptide hormone. This is a combination of FSH and LH derived from the urine of menopausal women. Administration is by intramuscular injection one to two times per day at a dose of 75 to 600 IU/day. This drug regime is also used to stimulate the ovaries in preparation for assisted reproductive technology (ART) procedures such as in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), or zygote intrafallopian transfer (ZIFT). It is said to be successful in stimulating ovulation in 85% to 90% of cases. It increases the multiple pregnancy rates up to 20% and increases the risk of both ovarian hyperstimulation syndrome and ovarian cancer. Side effects include mood swings and ovarian hyperstimulation.

When the diagnosis of hypothalamic dysfunction has been established and ovarian stimulation using Clomiphene citrate fails, the addition of gonadotrophin releasing hormone (GnRH), a hormone produced by the hypothalamus is administered. This is infused by pump into the indwelling and one side effect is potential infection of the indwelling line. This step is said to restore ovulation in nearly all cases. Restoring ovulation does not necessarily result in a successful pregnancy.

When elevated prolactin levels are causing amenorrhea or luteal phase defects are confirmed (e.g., in PCOS), bromocriptine is used. In this circumstance, thyroid function is also evaluated, as primary hypothyroidism can cause elevated prolactin levels. Many pharmaceutical drugs can also cause hyperprolactinemia as a side effect. This needs to be considered and ruled out. Hyperprolactinemia is treated using bromocriptine, a dopamine agonist. Administration is either oral or vaginally at doses of 2.5 mg twice daily or 0.5 mg twice a week. Bromocriptine does not increase the risk of inducing multiple pregnancies. Side effects include weakness, nausea, and nasal congestion.

Pelvic Factors

Endometriosis and the effects of salpingitis are the most common problems causing infertility related to pelvic factors. These affect the structural health of the fallopian tubes, as well as uterine and endometrial tissue. Salpingitis is usually caused by infections with microorganisms such as Neisseria gonorrhea and Chlamydia trichomatosis; other infective organisms include Escherichia coli, Mycoplasma hominis, and Ureaplasma urealyticum.⁷ Bacterial vaginosis is common among these women. Antibiotic drugs are the usual treatment for these infections.⁸ The treatment option for moderate and advanced endometriosis is usually surgical; at the time of a laparoscopy, resection and ablation is performed. Fibroids are usually left untouched and are only addressed if multiple miscarriages have been a problem. ART is available for those who are unable to conceive after surgery for common pelvic factors.

Cervical Factors

Inadequate cervical mucus midcycle is treated in one of two ways. Either low-dose estrogen is given mid to late in the follicular phase or human menopausal gonadotrophin (hMG) is given to stimulate ovarian production of estrogen. If this fails, the couples are recommended to artificial insemination (AI), one of the oldest of the fertility treatments still used. If cervicitis is a possible causal factor, the antibiotic doxycycline is administered. If surgery (commonly cone biopsy or laser ablation) or congenital issues render the endocervical glands absent or damaged, intrauterine insemination (IUI) procedures can result in pregnancy in 20% to 30% of cases within three cycles of treatment. Those who fail to have a positive outcome are offered the possibility of IVF, GIFT, or ZIFT.

Unexplained Infertility

When both partners’ evaluations yield negative results, this is defined as unexplained infertility. This is found in only 10% of cases.⁸ The main courses of treatment for couples with unexplained fertility include observation of the cycle and refining of timing techniques for intercourse, ovarian stimulation, IUI, GIFT, and IVF.

THE BOTANICAL PRACTITIONER’S PERSPECTIVE

Botanical treatment of infertility cannot address overt physical impediments to fertility; however, it can provide treatment and support for numerous fertility-related problems, such as hormonal dysregulation, thyroid and adrenal disorders, genitourinary infections, immune dysregulation, and stress-related problems (Table 12-2). The herbal consultation also takes into account factors such as nutritional deficiency and occupational/environmental exposures. Most importantly, a holistic practitioner reviews the case as a totality of contributing factors, not simply a reproductive issue.

TABLE 12-2 Botanical Treatment Strategies for Female Infertility

Fertility challenges should be approached as an opportunity for the couple to engage in an active treatment plan to improve their overall health, rather than just a quest for reproduction. Couples should be encouraged to participate in a 3- to 4-month period of preconception care, in which their overall health can be improved with the use of herbs, nutrition, and dietary and lifestyle modification. Thus, not only will they then improve their chance of natural conception, but they will be more likely to have a healthy, complication-free pregnancy and a healthy child. Additionally, for many couples, the attempt to conceive can become mechanical, lacking in passion, and plagued by a repeating cycle of expectation and disappointment. Ideally, botanical treatments for infertility attend to this problem, offering common sense and herbal strategies for restoring sensuality and passion to conception.

Herbal therapy requires a minimum commitment of 3 to 4 months to improve the fertility of a couple prior to conception, and in general, is ideally done when the couple is not concurrently taking any pharmaceutical fertility drug. Herbal medicines and nutritional supplements are prescribed for each individual situation, with appropriate dietary and lifestyle modification, stress management, and detoxification measures, if necessary (e.g., caused by environmental toxin exposure). The protocol should be revised on a regular basis (e.g., monthly) until conception occurs. If conception has not resulted after 12 months of holistic therapy, then other medical options may be considered. The treatment protocol in the remainder of this chapter focuses on botanical treatments for female fertility.

Herbs that enhance fertility might be divided into categories, and although they may overlap, they serve different purposes in nurturing reproductive health as well as general wellness. These categories include nutritive herbs that build the blood (e.g., rehmannia, dong quai) and support hepatic function (e.g., milk thistle), herbs that restore hormonal balance (e.g., chaste berry) and impart pelvic tone (e.g., shatavari), herbs that improve pelvic circulation (e.g., dong quai), and adaptogenic (e.g., ashwagandha), and nervine herbs (e.g., vervain), which help to reduce stress and improve the stress response.

Herbs can also be used externally in the form of essential oils to stimulate sexual desire (aphrodisiacs), and include amber, sandalwood, rose, jasmine, and ylang-ylang. A few drops can be carefully placed on the body (slightly diluted in a carrier oil such as almond oil), used in an atomizer to scent the air, sprinkled onto linens, or placed in a bath.

DISCUSSION OF BOTANICAL PROTOCOL

Black Cohosh

Black cohosh was thought to have estrogen-modulating activity and is used for both ovarian insufficiency affecting fertility and estrogen dominance affecting infertility (e.g., one factor in PCOS) (See Plant Profiles: Black cohosh for a discussion on the research and possible mechanisms of action). It has been described as a selective estrogen receptor modulator (SERM). It was a favorite herb of the native North American Indians and Eclectic physicians for amenorrhea, as a uterine tonic and a number of other gynecologic applications. 9 10 11 Black cohosh has been subjected to extensive clinical trials, demonstrating some estrogen-modulating activity and ability to reduce elevated LH levels, while not affecting FSH and prolactin in any way. In modern herbal applications, black cohosh is indicated for infertility associated with anovulation, PCOS, ovulatory pain, and secondary amenorrhea. Some common side effects have been noted, including a frontal headache with a dull, full, or bursting feeling and a low frequency of stomach complaints, including nausea and vomiting. These side effects are most likely with the high end of a therapeutic daily dose. Recent concerns have arisen that black cohosh may be associated with liver disease, including liver failure; therefore, caution should be observed with its use. (See Plant Profiles: Black cohosh.) It is recommended that this herb be avoided in pregnancy.

Chaste Berry

Chaste berry has a long history of use for regulating menstrual cycles, which may result from its ability to regulate prolactin levels, enhance corpus luteum development, and correct relative progesterone deficiency. Vitex is beneficial for ovulatory factors associated with infertility, in particular, modulating the anterior pituitary’s production of luteinizing hormone (LH), while mildly inhibiting follicle stimulating hormone (FSH). Vitex has been shown to downregulate the production of excess prolactin in hyperprolactinemia via dopaminergic activity.⁹^,¹² In an uncontrolled study, chaste berry reduced elevated prolactin levels in 80% of 34 women with hyperprolactinemia at a dosage of 30 to 40 mg per day for 1 month and improved symptoms of a variety of menstrual disorders, including secondary amenorrhea, cystic hyperplasia of the endometrium, deficient corpus luteum function, metrorrhagia, polymenorrhea, and oligomenorrhea.⁹ Chaste berry reduces thyroxin-releasing hormone (TRH)–induced prolactin release (essentially a pituitary–thyroid axis problem), normalizes shortened luteal phases, corrects luteal phase progesterone deficiencies, and reduces PMS symptoms in women with luteal phase defects caused by latent hyperprolactinemia. In two uncontrolled studies involving 45 infertile women with normal prolactin and pathologically low progesterone, 39 of the women achieved pregnancy after 3 months on chaste berry. In a second study involving 31 women with infertility, after 3 months 15 of these women were pregnant. Of these, seven women who became pregnant using chaste berry, seven previously had amenorrhea, four had luteal insufficiency, and four had been diagnosed with unexplained infertility.

Chaste berry should be considered a first-line botanical therapy for infertility associated with secondary amenorrhea, hyperprolactinemia, and luteal insufficiency, and should be given for a duration of at least 3 to 6 months. Chaste berry is particularly effective in restoring the menstrual cycle in a woman after years of taking oral contraceptive pills and improving low LH levels. The daily dose of chaste berry needed to improve ovulatory factors affecting fertility is 1 to 4 mL tincture or 500 to 1000 mg of dried berries daily. It is best taken as a single dose in the morning. Chaste berry is preferably not taken with other progesterone drugs and may interact antagonistically with pharmaceutical dopamine receptor antagonist drugs.

Dong Quai

Dong quai has been used in traditional Chinese medicine (TCM) as a female reproductive tonic, menstrual regulator, and remedy for amenorrhea for at least 20 centuries. Dong quai is regarded as a tonic for women with fatigue and low vitality. Traditional prescribing indicated dong quai for conditions of what is referred to as congealed blood evidenced by clots in the menstrual blood, endometriosis, and dark, sluggish menstrual flow, and is typically used in formulas to harmonize the blood. In one uncontrolled trial involving infertility resulting from tubal occlusion, a dong quai extract was administered via vaginal irrigation (douche) for up to 9 months. Approximately 80% of the women regained tubal patency and 53% became pregnant. The known constituents of dong quai include coumarins, essential oils, ferulic acids, psoralens, and vitamin B₁₂ and folinic acid, the active form of folic acid. Dong quai does not have estrogenic activity.

Dong quai is contraindicated for women with heavy bleeding and those with a history of spontaneous miscarriage. This herb is contraindicated for use with warfarin and anticoagulant medications, as it may increase bleeding time.

False Unicorn

False unicorn has been used historically as a female reproductive tonic, particularly for infertility and atony of the female reproductive organs. It was used by the Eclectic physicians as a uterine tonic to promote tone and vigor of the reproductive organs. For infertility, false unicorn is used when there is insufficient cervical mucus and amenorrhea. It was considered useful for congestion or stagnation of the uterus and ovaries, in which the menstrual blood is dark, sluggish, and clotted. Although not well characterized phytochemically, the steroidal saponins chamaelirin and diosgenin have been identified in false unicorn, and are postulated to exert an estrogen-modulating activity via interaction with estrogen receptor sites of the hypothalamus. There is no known toxicity or contraindication to use of false unicorn; however, this plant is a threatened species because of excessive wild harvesting and may soon be endangered. Therefore, this herb should only be used if other steroidal saponin–containing herbs such as tribulus and wild yam do not deliver a desired result and only when absolutely indicated.

Goldenseal

Goldenseal was the chief herb used by the Eclectics as a mucus membrane tonic. It was used for acute and subacute inflammation of the mucus membranes, especially when accompanied by discharge or mucus catarrh. It is valuable for the treatment for inflammation and infection of the genitourinary tract. The constituents include isoquinoline alkaloids, hydrastine, berberine, hydrastinine, and canadine. Hydrastis is a valuable remedy for ulceration, inflammation, and erosion of the cervix, affecting both quality and quantity of the cervical mucus. It can be used in both topical and internal applications.

Shatavari is a traditional Ayurvedic herb. The root is used medicinally. In the Indian medicine system, shatavari is said to “give her capacity to have a hundred husbands.”¹³ In traditional Ayurvedic gynecologic prescribing, shatavari has been used as a nutritive tonic, general female reproductive tonic, fertility tonic, treatment for sexual debility, and as an aphrodisiac. It has also been used traditionally as a tonic for lactating women to improve the quality and quantity of breast milk. Pharmacologic research has found the key constituents of shatavari are steroidal saponins, including shatavarin-I, alkaloids, and mucilage. The presences of the steroidal saponins suggest shatavari’s activity as an estrogen modulator and a menstrual cycle regulator. Shatavari has adaptogenic and immunomodulating properties and can be used as a very useful tonic herb for women with stress-induced and immune-mediated infertility. It has antibacterial action; hence, it should be considered a general reproductive tonic for any woman who has a history of genitourinary infections. There are no known contraindications to the use of shatavari. The daily dose is 4.5 to 8.5 mL of a dried plant extract.

Saw Palmetto

The Eclectic physicians used saw palmetto as a urinary and reproductive tract remedy for inflammation. It was widely used for ovarian pain, pelvic congestion, and atrophy of the ovaries. It proves to be a useful herb to include for infertility in cases of pelvic factors associated with infertility and infertility caused by PCOS. It is known to inhibit the production of prolactin from the pituitary.²⁰ If there is a history of genitourinary infection or pelvic inflammatory disease (PID), Saw palmetto is a valuable herb. The daily dose is 2 to 4 mL of a dried plant extract.

Tribulus

There is little information on the traditional use of tribulus leaf. In Ayurvedic medicine, the fruit has been used for improving male fertility and male erectile function, uterine disorders, urinary disorders, kidney stones, gout, and gonorrhea. As a result of Bulgarian research, tribulus has become a popular herb for the treatment of infertility, menopause, and low libido. It acts as a general tonic, aphrodisiac, and is used to restore vitality, reduce the physiologic effects of stress, and is a powerful fertility tonic for both men and women.⁹

Open-label clinical trials have demonstrated improvements in both male and female infertility.¹⁴ Bulgarian research has identified a unique steroidal saponin known as a furostanol saponin, calculated to no less than 45% protodioscin. The leaf is noted to be higher in the unique saponin than the fruit. Other active constituents include phytosterols and spirostanol glycosides. The results of studies and clinical trials with tribulus have been remarkable, both in animal and human models. When given at a dose of 750 mg per day for 5 days it increased serum FSH and estradiol when compared with baseline in females, and increased LH and testosterone in males, demonstrating an increase in sex hormone production for both men and women.⁹ The steroidal saponins are thought to bind and weakly stimulate the hypothalamic estrogen receptor sites. The tonic activities of tribulus have been shown to act by intensifying protein synthesis and enhancing the activity of enzymes associated with energy metabolism. It increases iron absorption from the small intestines and inhibits lipid peroxidation during stress. This leads to more muscle strength and improved endurance and stamina.⁹ Another stunning study showed that tribulus increased serum growth hormone, insulin, and aldosterone without exceeding normal values. Protodioscin, the steroidal saponin in tribulus, has been shown to improve sexual desire via the conversion of protodioscine to dehydroepiandrosterone (DHEA).¹⁵ It has been observed that tribulus grown in different soils does not consistently produce the important active furosterol, protodiocin. To ensure the desired clinical results, it is recommended to use only Bulgarian-grown tribulus standardized to 40% furosterol saponins by UV analysis. It is not interchangeable with Chinese or Indian tribulus. When samples of these were analyzed, they were shown to contain only 3% steroidal saponins by UV analysis, and none of these steroidal saponins are the unique and desirable furosterols. Specific female fertility studies have been conducted with tribulus. In an open study with 36 infertile women who were given tribulus on days 5 to 14 of the menstrual cycle for 2 to 3 months, 6% became pregnant as a result of normalized ovulation, 61% demonstrated normalized ovulation and no pregnancy, and 33% demonstrated no effect from tribulus within the 2- to 3-month time frame of the study.¹⁶ In this same study, another subgroup of women used tribulus concurrently with pharmaceutical ovarian stimulation with the drug epimestrol. Of the 62 women in this group, within 2 to 3 months, 39% had normalized ovulation and resultant pregnancy, 35% had normalized ovulation with no pregnancy, and the remaining 26% had no effect from the combined therapy. The results obtained from using tribulus concurrently with epimestrol were better than using the drug alone.

Although no increased frequency of fetal malformation or other harm has been observed in limited use by women during pregnancy, tribulus is considered contraindicated in pregnancy according to TCM, and in at least one animal study, decreased survival in the offspring of penned pregnant ewes fed the herb was observed.¹⁴ Animal studies of the minor alkaloid fraction of tribulus indicate that it inhibits acetylcholine, depressing activity of the frog heart in situ. The aqueous fraction produced mild hypotension. In dogs, an alcoholic extract of the whole plant produced a sharp vasodepression through a cholinergic mechanism.¹⁶ Ingestion of tribulus by sheep produced outbreaks of a locomotor disorder known as staggers, an asymmetric locomotor disorder in sheep produced by a central functional abnormality.¹⁷ Ingestion of tribulus caused photosensitivity in animals. No human or animal teratogenicity data are available, and scientific evidence for the safe use of tribulus during pregnancy is not available. The daily dose of tribulus is equivalent to 40 g per day of dried leaf or a concentrated extract standardized to contain a minimum of furostanon saponins as protodioscin at 300 to 400 mg per day. It is best used on days 5 to 14 of the menstrual cycle for enhanced fertility. It is essential to ensure phytoequivalence for optimal therapeutic outcomes. It is advisable to discontinue tribulus use during the luteal phase of the menstrual cycle, and to absolutely not resume use if pregnancy is suspected.

White Peony

White peony is commonly used in traditional Chinese and Japanese medicine for gynecologic conditions. It is generally used for infertility associated with PCOS, hyperprolactinemia, endometriosis, ovarian failure, and androgen excess. Paeonia has been shown to positively influence low progesterone, reduce elevated androgens (testosterone), and modulate estrogen and prolactin. In vitro, the active constituent paeoniflorin has been shown to affect the ovarian follicle by its action on the aromatase enzyme. Aromatase is important for follicular maturation, ovulation and corpus luteum function, steroid hormone synthesis, and the regulation of conversion of androgens to estrogens. The biofeedback in the pituitary and hypothalamus rely on aromatase to regulate prolactin and gonadotrophin-releasing hormone (GnRH). Excess levels of prolactin and GnRH inhibit the activity of aromatase. In TCM, Paeonia is always used in combination with other herbs. A TCM formula that contains Paeonia lactiflora and used in application for infertility is Keishi-bukuryo-gan (TJ-25) or Cinnamon and Hoelen Formula. One study with TJ-25 demonstrated, when used for 14 consecutive days in rats, increased plasma levels of LH by 94%, FSH by 67%, and estradiol by 50%. This formula is thought to be a GnRH antagonist and mildly antiestrogenic. When combined with Glycyrrhiza glabra, Paeonia lactiflora is effective at promoting fertility and improving pregnancy rates in cases of androgen excess, as learned from the TCM Licorice and Peony Formula.¹⁸ This combination regulated LH to FSH ratios.

Wild Yam

Wild yam has been used traditionally for uterine and ovarian spasm, including dysmenorrhea. When used for infertility it is employed to optimize estrogen levels and improve the quality and quantity of cervical mucus, if the cervical mucus is too viscous or too sparse. The active constituents of wild yam include the steroidal saponins dioscin and gracilin and soquinuclidine alkaloids such as dioscorine and tannins. It is useful as an antispasmodic to sooth oviductal and fallopian tube spasm, which can interfere with conception and implantation. For optimal bioavailability, the herb relies on adequate gut flora to enable to conversion of the steroidal saponin aglycone diosin to diosgenin. It is currently speculated that the bowel flora consumes a glycoside molecule from diosin, liberating diosgenin. Diosgenin is absorbed through the mucous membranes of the bowel into the bloodstream. Diosgenin may exert its effect by interaction at the hypothalamic estrogen receptor sites, regulating the production of estrogen by encouraging an increased production of FSH from the pituitary. Wild yam has demonstrated an estrogenic activity in vitro, and was shown to enhance estradiol by binding to estrogen receptor cites. Wild yam has no known side effects, interactions, or contraindications.

Immune Support

Immunologic factors affecting fertility are prevalent. Most cases result in recurrent spontaneous miscarriage; however, in some cases immunologic concerns prevent conception. The development of antisperm antibodies is one such circumstance. In study of 1020 female patients with primary or secondary infertility, serum antisperm antibody, antiovarian antibody, antiendometrial antibody, and anti-hCG antibody levels were tested. Patients were treated with dexamethasone, vitamin E, and vitamin C for three cycles consecutively as one course. After one course of treatment with corticosteroids, the disappearance rates of the antibodies mentioned were over 90%, and the average pregnancy rate was up to 30%. Corticosteroid use is associated with significant side effects.⁸ Herbs can be used either as an alternative first-line therapy or concurrently. An example of herb–drug synergy was seen when Glycyrrhiza glabra and cortisone ere successfully used together to minimize the dose dependence of the corticosteroid drug.⁹ Glycyrrhiza glabra has a cortisol-sparing action, as well as anti-inflammatory and adrenal restorative actions. It is contraindicated in hypertension, and steroid doses need to be modulated.

Rehmannia glutinosa is also of benefit in immune-mediated infertility and subfertility. Constituents in cured (cooked in wine) rehmannia, known as di huang, have been shown to inhibit antibody formation and reduce allergic reaction. Rehmannia has been shown to reduce the suppressive side effects of corticosteroid drugs on endogenous levels of corticosteroids and would be a valuable adjunctive therapy for a woman with immune-mediated infertility if already taking this drug therapy. It is sweet and warm in property and has been used to regulate menstruation and promote blood production, and is preferred in this application over the raw Rehmannia.

Echinacea is a well-known traditional immune-enhancing herb. It was widely used by Native Americans and then adopted by the Eclectic physicians for general immune support and infections. It is beneficial in the preconception stage of an infertility protocol to help immune surveillance. Echinacea can be aptly described as an immune modulator, assisting in enhanced phagocytosis and immune recognition. This may just be the key factor needed to regulate or prevent the onset of an autoimmune issue preventing conception or continued pregnancy. This action of echinacea is thought to be as a result of the presence of alkyl amides within the Echinacea root.¹⁹

Albizzia is a traditional Ayurvedic herb with antiallergenic properties. It has been shown to stabilize mast cells, reducing levels of allergy-inducing antibodies.²⁰ Although not phytochemically well defined, albizzia is a useful herb to support women who are producing antisperm antibodies.

NUTRITIONAL CONSIDERATIONS

Diet can play a significant role in fertility. Specific nutrients enhance normal reproductive function and fertility, thus assist in resolving conception problems when these are insufficient in the diet. These include zinc (found in pumpkin and sunflower seeds, brewer’s yeast, wheat germ, soybeans, eggs, seafoods, and meats), calcium (found in dairy products, leafy green vegetables, seaweeds, almonds, and blackstrap molasses), magnesium (found in whole grains, dark-green veggies, blackstrap molasses, nuts, and seafoods), vitamin C (found in citrus fruits, rose hips, cherries, currants, alfalfa sprouts, cantaloupe, strawberries, broccoli, peppers, and tomatoes), and folic acid (found in dark-green leafy vegetables, root vegetables, whole grains, milk, salmon, and brewer’s yeast). Essential fatty acids, found in wild cold water fish, most vegetable oils, flaxseed oil, evening primrose oil, borage oil, black current oil, are important for conception. In women who are very thin, with scanty or irregular periods or anovulation may be able to achieve cycle regularity, ovulation, and conception by gaining enough weight to bring them into a normal weight for height range.

Between 1990 and 1993, Foresight, a British medical association for the promotion of preconception, conducted a study using a nutritional and lifestyle modification preconception care program. The results were nothing less than remarkable. There was a tenfold reduction in the expected incidence of miscarriage and birth defects and over 80% success rate with unexplained infertility. It was evaluated that before the study was started, 60% of the women drank alcohol regularly and 57% of the women involved were previously smokers. Out of the 367 couples in the study, 327 (89%) of them successfully became pregnant and 327 children were born. All of these babies were born healthy. Among the 204 couples with infertility problems, 175 (86%) were able to achieve a healthy pregnancy.²¹ One of the most significant aspects of these results was the involvement of both partners in the program—both female and male factors were concurrently addressed. In addition to nutritional supplementation, the study included lifestyle and social modifications, including the cessation of smoking, and coffee and alcohol consumption. Smoking cigarettes and coffee consumption have been linked to subfertility and delayed conception. 22 23 24 Based on the Foresight study, the suggested preconception care nutritional program is outlined in Table 12-3.²¹

TABLE 12-3 Preconception Care Nutritional Supplementation

NUTRIENT	DAILY DOSE
Beta carotene	6 mg
Vitamin E	500 IU
Vitamin D	200 IU
B₁, B₂, B₃, B₅	50 mg each
B₁₂	400 μg
B₆	Up to 250 mg
Biotin	200 μg
Choline	25 mg
Inositol	25 mg
PABA	25 mg
Folic acid	500 mg
Vitamin C	2000–3000 mg
Bioflavonoid	300 mg
Calcium	800 mg
Magnesium	400 mg
Potassium	15 mg
Iron	15 mg
Iodine	75 μg
Selenium	100–200 μg
Zinc	20–60 mg
Chromium	100–200 μg
Omega-3 essential fatty acids (as Evening primrose oil)	500–1000 mg
Omega-6 essential fatty acids (as fish oil or flaxseed oil)	500–1000 mg

ADDITIONAL THERAPIES

Stress Management and the Mind–Body Approach

There is a direct relationship between fertility and stress is as much an endocrine experience as an emotional reality. The human body has extensive hormonal responses to the environment, especially stress, which occur at the hypothalamic and pituitary levels. The anterior pituitary is responsible for regulation of the female menstrual cycle. In response to stress, the adrenals release the hormone cortisol, known to adversely affect the menstrual cycle. The effects of stress are mostly associated with long menstrual cycles and delayed ovulation. Stress and elevated cortisol have also been linked to elevated prolactin levels. Stress management strategies should include lifestyle modifications, including exercise, yoga, and emotional release techniques. Physiologically, the hypothalamic pituitary adrenal (HPA) axis can be supported with adrenal tonic herbs such as licorice and rehmannia, in combination with adaptogenic herbs such as eleuthero (Eleutherococcus senticosus) and ashwagandha. These herbs act to regulate the HPA axis and assist in general adaptation syndrome. There is also increasing evidence that a behavioral approach might be effective in infertility treatment. A study of 54 women who completed a behavioral treatment program based on ability to elicit a relaxation response demonstrated decreased anxiety, depression, and fatigue. Additionally, 34% of the women became pregnant within months of completing the program. Behavioral therapy should be considered as therapy itself, or in conjunction with other treatments, including ART.²⁵

Addressing Environmental and Occupational Toxicity Associated with Infertility

Environmental and occupational toxicity has been linked to infertility, subfertility, spontaneous miscarriage, intrauterine growth retardation, and various birth defects, and is currently blamed for declining fertility. The particular

Formulas for Infertility: Various Associated Contributing Factors

Estrogen Balancing and Ovarian Tonic Formula (for follicular phase problems)

Chaste berry	(Vitex agnus-castus)	30 mL
Shatavari	(Asparagus racemosa)	30 mL
Schisandra	(Schisandra chinensis)	20 mL
Black cohosh	(Actaea racemosa)	10 mL
Wild yam	(Dioscorea villosa)	10 mL
Total: 100 mL

Dose: 5 mL three times daily

Luteal Insufficiency Formula

White peony	(Paeonia lactiflora)	50 mL
Chaste berry	(Vitex agnus-castus)	15 mL
Licorice	(Glycyrrhiza glabra)	25 mL
Blue cohosh	(Caulophyllum thalictroides)	10 mL
Total: 100 mL

Dose: 15 mL per day in the morning

Formula for Hyperprolactinemia

White peony	(Paeonia lactiflora)	25 mL
Ashwagandha	(Withania somnifera)	25 mL
Gymnema	(Gymnema sylvestris)	15 mL
Chaste berry	(Vitex agnus-castus)	12.5 mL
Licorice	(Glycyrrhiza glabra)	12.5 mL
Total: 100 mL

Dose: 5 mL three times daily

Formula for Elevated LH

White peony	(Paeonia lactiflora)	65 mL
Black cohosh	(Actaea racemosa)	35 mL
Total: 100 mL

Dose: 2 mL twice daily

Formula for Low LH

Tribulus *	(Tribulus terrestris)	60 mL
Chaste berry	(Vitex agnus-castus)	40 mL
Total: 100 mL

Dose: 20 mL twice daily.

Formula for Elevated FSH

Tribulus	(Tribulus terrestris)	80 mL
Shatavari	(Asparagus racemosus)	10 mL
Chaste berry	(Vitex agnus-castus)	5 mL
Wild yam	(Dioscorea villosa)	5 mL
Total: 100 mL

Dose:10 mL three times daily.

Formula for Elevated Testosterone/Androgens

Tribulus*	(Tribulus terrestris)	75 mL
Schisandra	(Schisandra chinensis)	10 mL
White peony	(Paeonia lactiflora)	10 mL
Licorice	(Glycyrrhiza glabra)	5 mL
Total: 100 mL

Dose: 10 mL three times daily.

Formula for Pelvic Factors/Uterine Tonic

White peony	(Paeonia lactiflora)	25 mL
Shatavari	(Asparagus racemosus)	25 mL
Saw palmetto	(Serenoa repens)	20 mL
False unicorn	(Chamaelirium luteum)	15 mL
Goldenseal	(Hydrastis canadensis)	15 mL
Total: 100 mL

Dose: 5 mL three times daily

Formula for Cervical Factors (sperm antibodies, mucous membrane integrity)

Rehmannia	(Rehmannia glutinosa)	25 mL
Echinacea	(Echinacea spp.)	25 mL
Wild yam	(Dioscorea villosa)	20 mL
Saw palmetto	(Serenoa repens)
Total: 100 mL

Dose: 5 mL three times daily

^* Because of the high dose requirements of tribulus, a concentrated extract in a tablet preparation is often more desirable for optimal patient adherence.

toxins linked to infertility include heavy metals, pesticides, environmental estrogens, volatile organic solvents, and radiation.²⁶^,²⁷ Heavy metals most often linked to subfertility are lead, mercury, and cadmium.²⁶^,²⁸

One study examined the association between occupational chemicals and radiation exposure in 281 infertile women compared with 216 fertile women. The study concluded there was an increased risk of infertility among women exposed to volatile organic solvents, chemical dust, pesticides, and video display terminals (radiation). The women exposed to volatile organic solvent and chemical dust had an increased incidence of ovulatory problems. Tubal factors and endometriosis were associated with solvents and chemical dusts. Endometriosis and cervical factor infertility were associated with exposure to video display terminals (radiation).²⁹

Environmental contamination is widespread; therefore, exposure to toxins is virtually ubiquitous. Research suggests the involvement of oxidative stress and electron transfer as the underlying causes of drastic health concerns such as infertility. The treatment framework should include multifaceted preventative measures, such as botanical and nutritional antioxidant therapy and liver support.³⁰ Herbal therapy with a focus on liver support and improvement of phase 1 and 2 liver detoxification are helpful in the preconception period and during the infertility treatment to aid effective conjugation of sex hormones and toxins. Herbs such as Silybum marianum, Schisandra chinensis, Picrorrhiza kurroa, and Burpleurum falcatum have demonstrated hepatoprotective and hepatorestorative activity and assist with improvement of liver function and the detoxification processes in the body.³¹ To protect against the damaging effects of radiation exposure, foods and herbs rich in antioxidants have been shown to protect and regulate gene activity. Herbs that exhibit antioxidant activity include Ginkgo biloba, Vitis vinifera, Silybum marianum, Rosmarinus officinalis, Camellia sinensis, and Curcuma longa.

Acupuncture and TCM

Acupuncture can be considered for women suffering from infertility and has been shown to be of benefit in those with luteal phase defects. In TCM, the diagnosis of kidney insufficiency is said to relate to luteal phase defects. Using acupuncture to regulate the kidney may help regulate the hypothalamus pituitary ovarian axis.³²^,³³

CASE HISTORY

A young couple had been trying to conceive for 28 months before seeking holistic therapy. They had been through one failed IVF attempt 6 months earlier, which motivated them to explore other options. The female was 30 years old, and from medical evaluation, the fertility complications resulted from female factors. The menstrual history has been normal with menarche at age 14 and a regular 34-day cycle. She was aware of texture changes to her cervical mucus and noted that she experienced fertile mucus on days 16 or 17 of the cycle each month and experienced cramps on the first day of her menses. Her general medical history included anxiety, depression, insomnia, and hypoglycemia.

Drug and Supplement History

She has been taking a prenatal folic acid B₁₂ supplement but was never advised by her medical doctor to take any other supplements. A few years prior, she took Prozac but discontinued this therapy because of side effects. She managed her depression and anxiety with counseling and regular yoga.

Reproductive History

Her reproductive medical history was complex and included hyperprolactinemia, a moderate degree of pelvic endometriosis, and mild cervical erosion with chronic inflammatory changes. She had a history of pelvic inflammatory disease associated with a Chlamydia infection that had been treated with doxycycline. Blood tests indicated progesterone failure with a late LH surge and elevated prolactin levels. She experienced premenstrual breast tenderness and mood changes on a monthly basis.

A previous laparoscopy, performed before the initial IVF attempt, revealed endometriosis and endometrial adhesions; her left ovary was tethered to the left broad ligament. During this procedure, the endometriosis was excised and ablated. A hysterosalpingogram before the IVF attempt revealed inflammation and edema in the fallopian tubes and some fallopian blockage. High-pressure oil perturbation was performed and bilateral tubal paltency was then established; her fallopian tubes were clear and apparently functional as of 18 months.

A previous postcoital test indicted she had been diagnosed with “hostile mucus,” with very few sperm moving in the mucus upon postcoital evaluation. Antisperm antibodies were detected in her mucus.

Additional Assessment

The client had regular lifestyle exposure to significant levels of radiation, including interstate and overseas flights five to six times per year, daily use of a cellular phone, recent spinal x-rays because of lower back pain, and daily exposure to video display terminals from working on a computer. She drank alcohol moderately (two glasses two to three times per week) and consumed 16 oz of coffee on a daily basis. Her diet was high in animal protein.

Treatment Protocol

Black cohosh	(Actaea racemosa)	15 mL
Ginger	(Zingiber officinale)	15 mL
White peony	(Paeonia lactiflora)	15 mL
Chaste berry	(Vitex agnus-castus)	15 mL
Goldenseal	(Hydrastis canadensis)	15 mL
Rehmannia	(Rehmannia glutinosa)	10 mL
Albizzia	(Albizzia lubbock)	15 mL
		Total: 100 mL