Clinical efficacy of Ayurveda treatment regimen on Subfertility with Poly Cystic Ovarian Syndrome (PCOS)

Abstract

Poly Cystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, resulting from insulin resistance and the compensatory hyperinsulinemia. This results in adverse effect on multiple organ systems and may result in alteration in serum lipids, anovulation, abnormal uterine bleeding and infertility. According to Ayurvedic view PCOS can be correlated with Aarthava Kshaya. It was revealed that most of subfertility patients who were presented Osuki Ayurveda Centre suffered from the PCOS. Therefore the present study was carried out for the clinical evaluation of the efficacy of Ayurveda treatment regimen on subfertility with PCOS. Total 40 patients were selected by using purposive sampling method. According to the Ayurveda theories of Shodhana, Shamana and Tarpana, the treatment was conducted in 3 stages for the duration of 6 months. The response to the treatment was recorded and therapeutic effects were evaluated by symptomatic relief and through Trans Vaginal Scan and LH, FSH hormone levels. The results revealed that, subfertility due to PCOS can be cured successfully by using this Ayurveda treatment regimen.

Keywords: Aarthava Kshaya, Subfertility, Poly Cystic Ovarian Syndrome

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Introduction

Poly Cystic Ovarian Syndrome is a relatively common endocrine disorder in women of reproductive age group. It is found in around 70% of women who have ovulation difficulties leading to subfertility.

Poly Cystic Ovarian Syndrome is a condition that has cysts on the ovaries that prevent the ovaries from performing normally. Symptoms of Poly Cystic Ovarian Syndrome include Amenorrhea or infrequent menstruation, irregular bleeding, infrequent or no ovulation, multiple immature follicles, increased levels of male hormones, male pattern baldness or thinning hair, excess facial and body hair growth, acne, oily skin or dandruff, dark coloured patches of skin specially on neck, groin, underarms, chronic pelvic pain, increased weight or obesity, diabetes, lipid abnormalities and high blood pressure1.

Fertility problems experienced by women with Poly Cystic Ovarian Syndrome may be related to the elevated hormone, insulin or glucose levels, all of which can interfere with implantation as well as development of the embryo1. Increased Leutenizing hormone reduces the chance of conception and increase miscarriage. Additionally abnormal insulin levels may also contribute to poor egg quality, making conception more difficult1.

It is estimated the 50 - 60% of women who presented to the Osuki Ayurveda Centre for subfertility treatment were with Poly Cystic Ovarian Syndrome for the last 2 years. There is a special Ayurveda treatment regimen used in Osuki Ayurveda centre to cure Poly Cystic Ovarian Syndrome. Observing for nearly a period of two years of this treatment regimen, it is understood that this treatment regimen has a powerful effect for the management of Subfertility with Poly Cystic Ovarian Syndrome. But so far no scientific studies was carried out; hence the present study was carried out to scientifically evaluate the efficacy of this Ayurveda treatment regimen in subfertility with Poly Cystic Ovarian Syndrome.

Material and Methods

Preparation of drugs: All medicines were prepared by “Beem” chemicals under supervision of the principal author.

Clinical study: In the present study, 40 patients of subfertility with Poly Cystic Ovarian Syndrome were selected from Osuki Ayurveda Centre, Rajagiriya, Sri Lanka.

• These patients were subjected to detailed clinical examination and investigations specially FSH, LH level and its ratio, Testosterone, FBS, Lipid profile, Liver function test and USG.

Criteria for diagnosis:

The presence of at least 3 of the following criteria:

• Polycystic Ovaries on USG
• Oligomenorrhea or anovulation
• Clinical or bio-chemical evidence of Hyperandrogenism
• Elevated LH
• LH: FSH ratio > 3 and

25 - 40 years age grouped subfertility patients were selected to the present study. The patients suffering from diabetes mellitus, hypertension, thyroid disorders, hyper prolactinemia, congenital adrenal hyperplasia, other gynaecological disorders, heart diseases and renal failure were excluded from the research. The male partners of selected couples had neither any abnormalities in Seminal Fluid Analysis nor any condition which leads subfertility.

The treatment was conducted in 3 stages for duration of 6 months.

In stage 1 (Day 1 to day 14) patients were treated with 30ml of Triphala Kwatha, 2 pills of Chandraprabhaand 5g of powder of Manibhadra twice a day in the morning and evening at 6 PM. These drugs were administrated to do the basic body purification of the patients and also all these drugs are favourable to the function of the female genital organs2.

In stage 2 (Day 15 to 4th month) patients were treated with 5g of each powder of Shatavari (Asparagus racemosus), Shatapushpa (Peucedanum graveloens) and Guduchi (Tinospora cordifolia) twice a day in the morning and evening. Further they were treated with 20ml of Krishna Jeeraka, twice a day in the morning and evening. Shatavari is used to correct the hormonal influence and enhance the follicular maturity.Guduchi is used to increase the immunity (“Ojas”) of the patients. Shatapushpa act as a follicular maturity substance and as a pain relief agent. It also acts against menstrual irregularity3,4.

In stage 3 (4th to 6th month) patients were treated with 5g of each powder of Atibala (Abutilon indicum) andShatapushpa and 4 pills (each 125mg) of Rasayana Kalpa (A. racemosus, Terminalia chebula, T.belarica, Embelica officinalae, T. cordifolia, Naredostachys jatamansi, Herpestis monnieria) twice a day in the morning and evening at 6 PM4. Further they were treated with 20ml of oil of Sahachara twice a day in the morning and evening at 8 PM. These patients were locally treated with Uttara Vasti with 5ml of oil ofShatapushpa two consecutive days per month from the day which is completely cessation of the menstrual flow in between 4th to 10th day of the cycle. Atibala is used to correct the hormonal disturbances and facilitates to avoid miscarriages. Sahachara is used to remove unwanted follicles.

The responses to the treatment were recorded and therapeutic effects were evaluated by symptomatic relief and through Ultrasonography and LH/ FSH hormones. Ultrasonography views the changes of the ovaries and the changes of the follicles regarding to the treatment. FSH/LH ratio is showing the reappearance of the hormonal levels to normal range. Pregnancy confirmed by using urine hCG test.

 

Observation and Results

These patients differ from each other in many ways such as physique, temperament and habits. In the present study all the patients were housewives and all they have no considerable stressful life style. They all suffered from primary subfertility and 90% of them have 4 to 6 years of marriage life.

The 80% of patients were not using any contraceptive method while 10% used oral contraceptive pills and 5% used condom and natural methods, for the treatment of 6 months or less. All patients have not taken any kind of medicine within one year for PCOS and subfertility.

They complained mostly irregular, few or absent menstruation, scanty or less menstrual blood, pain in menstruation, duration of menstruation below 3 days, excessive and increased body hair in face and chest, skin discolouration and obesity.

Assessment criteria were based on the improvement in the score of cardinal symptoms which are irregular menstruation, duration of bleeding, dysmenorrhea, quantity of menstrual blood, excessive body hair, obesity, and skin discolouration before and after the treatment. The improvement in the cardinal symptoms were compared and analyzed statistically between the end of the treatment and baseline by using student's paired ‘t’ test.

USG reports revealed, that reduce of polycystic appearance of ovaries and improvement of follicular maturity. LH/ FSH hormone reports revealed that the ratio came to the normal level.

Assessment of amount of bleeding

All the pads were collected and subjected to assessment of menstrual blood loss before during and after treatment. The method used by Vaishali Shinde (2004) in India was used for this study to measure the weight of pads. No. of pads were counted by using a pictorial chart, as used in previous studies by Higham in 1990 and Herve Ferdinandez in 2003.

At the end of the aforesaid Ayurveda treatment regimen 85% of the patients were successfully get cured from Poly Cystic Ovarian Syndrome, while 75% of the patients get conceived.

 :

Discussion

Poly Cystic Ovarian Syndrome is one of the main causes of subfertility in women. It is associated with anovulation, androgen excess, obesity and subfertility. PCOS results in increased free testosterone, ovarian androgen secretion, free estradiol and estrone. It's favouring LH secretion and steady state follicle stimulating hormone levels which effect on follicular maturation. This hyperandrogenic, normoestrogenic environment results in an anovulatory state, no progesterone is available to disrupt the constant estrogen stimulation of the endometrium1,5.

Table 1

Duration of bleeding

Table 2

Irregular Menstruation

Table 3

Amount of bleeding & quantity of Menstrual blood

Table 3 (1)

Quantity of Menstrual blood

Table 4

Pain during Menstrual period

Table 5

General weakness

Table 6

Prognosis of the cardinal symptoms

Table 7

Overall effect of the therapy

In allopathic medicine oral contraceptives, progestins, anti androgens and ovulation induction agents remain standard therapies.

Aartava-kshaya, which can be correlated with PCOS has been described as deficiency or loss of artava, artava dose not appears in time or is delayed, is scanty and dose not last for three days. Pain in vagina also can be seen. According to Ayurveda, Aartava-kshaya is a disorder involving Pitta and Kapha doshas, Medas, Ambu/Rasa, Shukra/Artava Dhatu and Rasa, Rakta, Artava Vaha Srotas6. Therefore Poly Cystic Ovarian Syndrome can also be described with same involvement of Dosha, Dhatu and Upadhatu Kaphapredominance manifests as increased weight, subfertility, hirsutium, diabetic tendencies and coldness. Pittapredominance manifests as hair loss, acne, painful menses, clots and heart problems. Vata predominance manifests with painful menses, scanty or less menstrual blood and severe menstrual irregularity6,7,8.

The pathology is an obstruction in the pelvic cavity (Apana Kshetra) causing disorders in the flow of Vata. This in turn leads to an accumulation of Kapha and Pitta.

The treatment principle is to clear obstruction in the pelvis, normalize metabolism and regulate the menstrual system (Aartava Dhatu). Kapha reducing, insulin enhancing and hormone rebalancing drugs help to the relieve symptoms of Poly Cystic Ovarian Syndrome.

Triphala Kwatha, Chandraprabha Vati and Manibhadra Choorna help to clear obstruction and normalize the srotas. Especially Triphala and Guggulu are very useful for reducing excess weight2.

Powder of A. racemosus brings balance and strength to the menstrual system and it helps to regulate Aartva Dhatu. Properties of Powder of seeds of P. graveloens, oil of Krishna Jeeraka (Nigella sativa) and oil ofSahachara (Barleria prionits) were helped to destroy cysts on ovaries and stimulate the follicular maturity. Properties of Deepana and Pachana of above drugs they elevate the Jatharagni, Dhatvagni as well asAartavagni2. Powder of Guduchchadiya enhances the overall immunity and powder of Atibala has properties of Prajasthapana, Garbhasya DaurbalyAhara, Balya, Brunhana and Ojo Vardhana2. Therefore it helps to get conceived and avoid miscarriage3,5.

Uttara Vasti is the most effective treatment in gynaecological disorders. It helps to purification and clears theAartava Vaha Srotas, pacifies vitiated Apana Vayu8 and improve follicular maturity.

Due to Samprapti Vighatana Kriya of this Ayurveda treatment regimen the symptoms of Poly Cystic Ovarian Syndrome get reduced. The effect of therapy show highly significant result on all above symptoms of Poly Cystic Ovarian Syndrome. When considering irregular menstruation most of the patients had 2 - 4 months duration. At the end of the treatment irregularity showed only 25% of the patients. At the end of the treatment 57.5% of patients had normal duration of menstrual bleeding, 75% of patients were relieved from Dysmenorrhea and majority of patients (70%) had average quantity of menstrual blood. When considering skin discolouration, 87.5% of patients were relieved from the symptom.

At the end of the treatment, majority of patients (85%) had normal BMI levels. But when considering the symptom of excessive and increased body hair, there was no significant relief shown.

In case of subfertility with Poly Cystic Ovarian Syndrome, 85% of patients were successfully get cured from Poly Cystic Ovarian Syndrome, while 75% of patients were conceived.

All these patients were followed for the period of one year. During that period uncured patients were treated continuously. After the four month of duration 90% were cured. The pregnant mothers were treated with Prajasthapana drugs during their ante-natal visits to the clinic. All of them delivered healthy babies. At the end of this follow up period 85% from the treated group were conceived.

Conclusion

In conclusion, subfertility due to Poly Cystic Ovarian Syndrome can be cured successfully by using aforesaidAyurveda treatment regimen.

References

1. Dutta D.C. Text book of Gynaecology. 4th edition. Culcutta: New central book Agency LTD; p. 421. (431, 523, 549, 558).

2. Ayurveda Pharmacopoeia Vol I part I. Department of Ayurveda. 1985:173.

3. Ibid (2), part III. (82, 110, 177, 235, 269, 305, 313, 321, 344, 358).:25.

4. Jayaweera D.M.A. Medicinal plants (Indigenous and Exotic) used in Ceylon. The National Science Council of Sri Lanka. 1981 Part-I, 9,11pgs, Part-V, pg. 149, Part-IV, pg. 81.

5. 2007. Dec 14th, http://en.wikipedia.org/wiki/Polycystic_ovary_syndrome .

6. Tewari P.V. Ayurveda Prasuti Tantra Evam Stri Roga, Stri Roga, Chaukambha Orientale. Varanasi: 1996. p. 169. (192). Part-II.

7. Sharma P.V. Charaka Samhita (English Translation) Chaukambha Orientalia. Varanasi: 1981.

8. Srikantha Mruthi K.R. Sushruta Samhita (English Translation) Chaukambha Orientale. Varanasi: 2001. pp. 170–173.

Courtesy of Medknow Publications

Assessing Egg Quantity with Anti-Mullerian Hormone

Is there hope for infertile women with diminished ovarian reserve?

Abstract

Diminished ovarian reserve, a natural process by which the follicular pool diminishes with time, is often clinically asymptomatic but presents a challenge to those wanting to become pregnant. Although pelvic ultrasonography and day 3 serum hormone testing have long been common methods of assessing ovarian reserve, promising research suggests the utility of anti-mullerian hormone testing to identify patients with diminished ovarian reserve. Conventional wisdom would suggest that in vitro fertilization is the only answer for diminished ovarian reserve, but preliminary research offers hope that egg quality and ovarian reserve can be improved by dehydroepiandrosterone, melatonin, and myo-inositol.

Introduction

Infertility is often initially evaluated in the primary care setting after 12 months of regular, unprotected intercourse in women younger than age 35, and after 6 months of regular intercourse in women older than age 35.1 Evaluations can be initiated earlier in women with irregular cycles, suspected anovulatory cycles, or other known risk factors for infertility, such as endometriosis, polycystic ovaries, or a history of pelvic inflammatory disease. Both partners should undergo a complete evaluation concurrently, since multiple factors can affect fertility. Poor semen parameters, anovulation, tubal disease, poor egg quality, and endocrine imbalances are some of the causes of infertility, each with its own treatment approaches.

Diminished ovarian reserve (DOR) is a natural phenomenon in which the number and quality of a woman’s eggs diminish as she ages in a process called atresia. The loss of the primordial egg pool begins at 20 weeks of gestation, and by menarche, the primordial egg pool contains an estimated 500,000 follicles.2 As the follicular pool wanes with time, female fecundity (ie, ability to reproduce) diminishes. A woman is said to have a diminished ovarian reserve when her follicular pool is less than what is expected for her age. Whether due to the physiologic aging of the ovaries or premature ovarian aging, diminished ovarian reserve is often clinically asymptomatic and represents one of the most challenging infertility diagnoses to overcome.

Evaluating Ovarian Reserve

Reproductive endocrinologists assess ovarian reserve through a number of diagnostic tests. One such test is the pelvic ultrasound performed early in the menstrual cycle to evaluate the number of follicles present. The more follicles present (known as the “antral follicle count”), the greater that patient’s ovarian reserve. Pelvic ultrasonography, although a useful diagnostic tool, is highly user-dependent and is not available for use in primary care and naturopathic medical clinics. Another means of assessing ovarian reserve is through serum hormone testing. Historically, the most common serum tests to assess egg quality have been follicle stimulating hormone (FSH) and estradiol on day 3 of the menstrual cycle. FSH is a measure of how much stimulation the ovaries require to function. An FSH measurement greater than 10–12 mIU/mL has been identified as the upper limit of normal,3 whereas estradiol greater than 80 pg/mL is considered the upper limit of normal.4 Estradiol is measured concomitantly with FSH in part to determine the validity of FSH testing. If estradiol is elevated, FSH is suppressed, and this can appear as a falsely normal or low FSH level. The accuracy of day 3 serum evaluation is affected by endogenous hormone production (such as a functional ovarian cyst producing estrogen), exogenous hormones (such as infertility medications), and the timing of the sample collection.5

Overall, AMH demonstrated the strongest inverse correlation with the number of retrieved oocytes.

 

In the last several years, anti-mullerian hormone (AMH) testing has been studied for use in the assessment of egg quantity. AMH is a peptide hormone from the TGF-β family made from birth to menopause by the functional granulosa cells of the preantral follicles. Therefore as the preantral follicle count diminishes with time, AMH levels diminish as well.6,7 In addition, serum studies have demonstrated that AMH levels are stable throughout the menstrual cycle and demonstrate minimal variability between menstrual cycles.8–11 A recent retrospective study in the American Journal of Obstetrics and Gynecology compared the number of oocytes retrieved during a given round of in vitro fertilization (IVF) with AMH, inhibin B, day 3 estradiol, and day 3 FSH.12 No correlation was seen between the number of oocytes retrieved and inhibin B, but AMH, FSH, and estradiol demonstrated statistically significant inverse correlation with the number of oocytes retrieved. Overall, AMH demonstrated the strongest inverse correlation with the number of retrieved oocytes.12 Riggs et al established a sensitivity of 83–84% and specificity of 67–79% using ROC curve analysis data.13 In addition, Barad et al, in a study investigating the utility of age-specific AMH, determined that AMH provides the best specificity for diminished ovarian reserve in women ages 32–39;14 however, the same team concluded that AMH testing is particularly beneficial for younger women because diminished ovarian reserve is often unsuspected in younger women, leading to the inaccurate diagnosis of “unexplained infertility.” A growing number of retrospective and prospective data corroborate the utility of AMH as a marker for ovarian reserve.15–24

Despite its value in assessing ovarian reserve, AMH testing has several shortcomings. First, there is no uniform reference range for interpreting AMH levels in regard to ovarian reserve, largely because different laboratories use different assays (see Table 1 and Figure 1). Gnoth et al determined an AMH of less than 1.26 ng/ml denotes a diminished ovarian reserve regardless of age.25 Ebner et al determined that an AMH between 1.7 and 4.5 ng/ml results in maximal egg quality.26Tremellen et al defined diminished ovarian reserve as an AMH less than 0.8 ng/ml, which they specify is comparable to an FSH of 11 mIU/ml.27 Second, despite an emergence of promising research on the correlation of AMH with ovarian reserve and egg quality, there is conflicting data regarding the correlation of AMH with pregnancy rates.21,28,29 Notwithstanding, a study conducted by Barad et al demonstrates that AMH is superior to FSH in predicting IVF outcomes.30 And lastly, there is now some emerging research demonstrating that AMH levels can be influenced by race, body mass index, and polycystic ovaries.31,32,33 Some preliminary research has shown that women with polycystic ovaries have AMH levels 2- to 3-fold higher than women with ovulatory cycles.34 AMH studies controlling for these variations are pending. Given the emerging data demonstrating the utility and convenience of AMH testing, it should be routinely considered in the diagnostic evaluation of all infertile women to determine ovarian reserve. 

Treatments

There is very little research demonstrating strategies to improve ovarian reserve. Conventional wisdom would question whether or not that is even plausible. However, some preliminary data on the use of dehydroepiandrosterone, melatonin, and myo-inositol offers hope for women with diminished ovarian reserve. 

Dehydroepiandrosterone (DHEA)

The first study demonstrating potential improvement in ovarian reserve with dehydroepiandrosterone (DHEA) supplementation was published more than a decade ago. Casson et al presented data documenting the positive effect of DHEA supplementation on oocyte yields in patients with a prior history of poor response during IVF cycles.35 The effect was caused by increasing IGF-1 and augmenting the effects of gonadotropin medications. In an attempt to further elucidate the mechanism by which DHEA improved egg quality, Sen and Hammes conducted a mouse study showing that DHEA increases androgens that regulate ovarian development and function by promoting preantral follicular growth and preventing follicular atresia.36 Initial attempts to reproduce human studies in patients with DOR have proven challenging due to the fact that many infertility patients decline randomization during the initial trial phase, due to concerns about wasting precious time. Barad and Gleicher are conducting much of the latest research on DHEA use during IVF; they recommend compounded micronized DHEA at a dose of 25 mg tid for at least 6–8 weeks before initiating an IVF cycle, with effects plateauing after 5 months of supplementation.37–39 Instead of a randomized controlled study, Barad and his team documented the effects of pre- and post-DHEA IVF cycles. In 25 women diagnosed with DOR, DHEA supplementation improved the numbers of oocytes retrieved, fertilized oocytes, day 3 blastomeres, transferred embryos, and normal day 3 embryos.40 In a follow-up study, Barad found that when 89 DOR patients supplemented with DHEA for up to 4 months, they had a shorter time to pregnancy, as well as higher pregnancy rates when compared to 101 controls (pregnancy rate of 28.1% in DHEA-supplemented women vs 10.9% in controls).39 When age-dependent DOR patients and patients with premature ovarian aging are separated and compared, it appears as though DHEA is similarly effective in both groups.39 The latest study, conducted by Gleicher et al, demonstrated that women taking DHEA had improvement in AMH, which also correlated with increased pregnancy rates.38 Gleicher also suggests that DHEA may reduce aneuploidy in oocytes and embryos,41 thus improving pregnancy rates. Wiser et al have demonstrated similar effects of DHEA supplementation, also using a dose of 25 mg tid.42 Recently and most surprisingly, Gleicher and Barad documented a spontaneous pregnancy in a 38-year-old patient with premature ovarian failure after 4 months of DHEA supplementation, her highest FSH previously being 100.0 mIU/mL. They are now investigating DHEA supplementation in patients with premature ovarian failure, with results to be published after 2013.14 Barad and Gleichner have also documented that women taking DHEA complain of very few side effects; the most common adverse effects reported with DHEA use are oily skin, acne vulgaris, and mild hair loss.38 Other studies have corroborated that hirsutism and acne are the most commonly reported side effects of similarly dosed DHEA, while oral stomatitis, myalgias, headaches, irritability, and nausea are less common complaints.43 

Melatonin

Melatonin has been studied as an antioxidant, free-radical scavenger, and nutrient that can modulate gene transcription for antioxidant enzymes.44–47 There is some evidence that reactive oxygen species are made by the follicles during ovulation and that there is less glutathione reductase in the follicular fluid of infertile women.48,49 In an effort to investigate the relationship between oxidative stress and egg quality, Tamura et al studied the effect of melatonin supplementation in infertile women with poor egg quality. Women who had failed their first round of IVF were divided into 2 groups before initiating their second round of IVF; 56 women received melatonin supplementation (3 mg per day) and 59 women received no melatonin. Women who received melatonin supplementation had slightly improved pregnancy rates, although this trend was not statistically significant.50 Recently a placebo-controlled study conducted by Batioglu et al compared the effects of administering 3 mg/day of melatonin (n=40) versus no treatment (n=45) to age-matched women undergoing IVF. Women who received melatonin supplementation had modest improvement in the percentage of mature oocytes retrieved, embryo quality, and clinical pregnancy rate. Although the difference was not statistically significant, Batioglu et al speculate that melatonin has a positive impact on oocyte and embryo quality.51 More research on melatonin use for DOR is warranted to ascertain if it is an effective treatment option to improve ovarian reserve. 

Myo-inositol 

Myo-inositol, an isomer of inositol made from glucose-6-phosphate, has been said to improve insulin sensitivity and oocyte maturation.52 Myo-inositol has been shown to be an important constituent in the follicular microenvironment wherein higher levels of myo-inositol in the follicular fluid have been correlated to improved egg quality.53,54 Papaleo et al studied 60 infertile women undergoing IVF; they were given 2 grams of myo-inositol twice daily with 400 mcg folic acid (n=30) or 400 mcg folic acid alone (n=30). Cycles were canceled when E2 levels exceeded 4,000 pg/ml as this indicates a higher risk for ovarian hyperstimulation syndrome. Women in the group receiving myo-inositol required a lower dose of ovarian stimulation medication, had lower peak E2 levels, and had a decreased mean number of immature oocytes. Only 1 cycle had to be canceled in the group receiving myo-inositol, whereas 3 cycles were canceled in the control group due to elevated E2 levels. Although there was no statistically significant difference in the pregnancy rate between the myo-inositol group (11 pregnancies) and the control group (10 pregnancies), their findings suggest myo-inositol supplementation has a positive impact on oocyte development and maturation.55 A similar double-blind study was conducted in Italy in which women diagnosed with polycystic ovaries were given 2 grams of myo-inositol with 200 mcg folic acid twice daily or 200 mcg folic acid alone twice daily for 3 months. During ovarian stimulation protocols, women who had taken the myo-inositol had more follicles measuring greater than 15 mm on ultrasonography, a greater number of oocytes recovered at retrieval, and a greater number of embryos suitable for transfer, suggesting that myo-inositol can influence ovarian reserve and egg quality.56

Conclusion

Given the aforementioned data on natural therapies for improving ovarian reserve, DHEA has the most compelling positive research demonstrating improvement in ovarian reserve. Although melatonin and myo-inositol demonstrated some improvement, the effects were not statistically significant and therefore these supplements should only be offered if a patient is not tolerating side effects of DHEA supplementation, until further research is conducted.

 

 References

1.  Reproductive Endocrinology and Infertility Committee, et al. Advanced reproductive age and fertility. J Obstet Gynaecol Can.2011;33(11):1165-75.
2.  Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod. 1992;7:1342-46.
3.  Barad DH, Weghofer A, Gleicher N. Age specific levels for basal follicle-stimulating hormone assessment of ovarian function. Obstet Gynecol. 2007;109:1404-10.
4.  Smotrich DB, Wildra EA, Gindoff PR, Levy MJ, Hall JL, Stillman RJ. Prognostic value of day 3 estradiol on in vitro fertilization outcome.Fertil Steril. 1995;64(6):1136.
5.  Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-Mullerian hormone: a new marker for ovarian function. Reproduction. 2006;131:1-9.
6.  Ibid
7.  Weenan C, Laven JS, Von Bergh AR, et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10:77-83.
8.  Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, Te Velde ER, Broekmans FJ. Anti-Mullerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab. 2006;91:4057-63.
9.  La Marca A, Stabile G, Artenisio AC, Volpe A. Serum anti-Mullerian hormone throughout the human menstrual cycle. Human Reprod.2006;21:3103-7.
10.  Tsepelidis S, Devreker F, Demeestere I, Flahaut A, Gervy Ch, Englert Y. Stable serum levels of anti-Mullerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women. Human Reprod. 2007:22:1837-40.
11.  Fanchin R, Taieb J, Lozano DH, Ducot B, Frydman R, Bouyer J. High reproducibility of serum anti-Mullerian hormone measurements suggest multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status. Human Reprod. 2005;20:923-7.
12.  Riggs RM, Duran EH, Baker MW, et al. Assessment of ovarian reserve with anti-Mullerian hormone: a comparison of the predictive value of anti-Mullerian, follicle-stimulating hormone, inhibin B, and age. Am J Obstet Gynecol. 2008;199:202.e1-202.e8
13.  Ibid
14.  Barad DH, Weghofer A, Gleicher N. Utility of age-specific serum anti-Mullerian hormone concentrations. Reprod BioMed. 2011;22:284-91.
15.  Seifer DB, MacLaughlin DT, Christian BP, Feng B, Sheldon RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril. 2002;77:468-71.
16.  de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC, Anti-Mullerian hormone serum levels: a putative marker for ovarian aging.Fertl Steril. 2002;77:357-62.
17.  van Rooij, Broekmans FJ, te Velde ER, et al. Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod. 2002;17:3065-71.
18.  Tremellen KP, Kolo M, Gilmore A, Lekamge DN. Anti-Mullerian hormone as a marker of ovarian reserve. Aust N Z J Obstet Gynaecol.2005;45:20-4.
19.  Eldar-Geva T, Ben-Chetrit A, Spitz IM, et al. Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome. Human Reprod. 2005;20:3178-83.
20.  Muttukrishna S, McGarrigle H, Wakim R, Khadum I, Ranieri DM, Serhal P. Antral follicle count, anti-Mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology? BJOG. 2005;112:1384-90.
21.  Kwee J, Schats R, McDonnell J, Themmen A, de Jong F, Lambalk C. Evaluation of anti-Mullerian hormone as test for the prediction of ovarian reserve. Fertil Steril. 2007.
22.  Singer T, Barad DH, Weghofer A, Gleicher N. Correlation of anti-Mullerian hormone and baseline follicle-stimulating hormone levels.Fertil Steril. 2009;91:2616-19.
23.  La Marca A, Volpe A. Anti-Mullerian hormone in female reproduction: is measurement of circulating AMH a useful tool? Clin Endocrinol. 2006;64:603-10.
24.  Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril. 2011;95:747-50.
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Premature Ovarian Failure

Ovarian failure is considered premature when it occurs in women < 40 yrs of age and accounts for 10 % of secondary amenorrhoea which means failure of occurrence of menstruation in women for 6 months or longer in women who have previously menstruated. 

The term used is Primary Ovarian Insufficiency and has replaced premature ovarian failure and premature menopause in recognition that this disorder represents a continuum of decreased ovarian function.

 
Menstruation is an end point in the cascade of events starting in the cerebral cortex and hypothalamus and through pituitary gland and ovaries ending with uterine bleeding with a patent lower genital tract. A disturbance at any level can cause amenorrhoea. 

Primary ovarian insufficiency results from a loss of negative feedback restraint on the hypothalamus and pituitary, resulting in increased FSH and LH levels which are the Follicle Stimulating Hormone and Luteinizing Hormone respectively. FSH is a better marker as its levels are less variable than LH.

Levels may wax and wane and hence serial measurements are necessary for the diagnosis.

Causes of Premature Ovarian Failure
• Chromosomal abnormalities including Turner Syndrome
• Autoimmune diseases are reported in 30-60% of patients. Mumps, thyroid dysfunction, hypoparathyroidism, and Addison s disease can be responsible in some cases.
• Tuberculosis of the genital tract.
• Smoking. 
• Radiotherapy and Chemotherapy are causes but the effect can be reversible and the ovaries can start functioning after a year or two of stopping the treatment.


• Can follow hysterectomy or tubectomy. 
• Galactosemia
• Premutation carriers of Fragile X syndrome- Risk of severe mental retardation in male children with FMR1 mutations.
• Idiopathic or unknown cause.
• Rarely in mutations of FSH and LH receptors
• Aromatase deficiency 
• 17-hydroxylase deficiency
• Prolonged GnRH therapy 
• Induction of multiple ovulation in infertility can cause premature menopause when the follicles get exhausted.

Clinical Features In Premature Ovarian Failure
• Amenorrhoea
• Hot flushes
• Sweating
• Headache
• Irritability
• Depression
• Lack of concentration
• Insomnia
• Diminished libido
 

Detox Element in Diet may Help Determine Women's Fertility

The role played by the natural antioxidant selenium at the earliest stages of a woman's fertility has been highlighted in a University of Adelaide research.

The discovery has been made in joint research involving the University's School of Chemistry and Physics and the Robinson Research Institute. 

For her PhD in Chemistry at the University of Adelaide, Melanie Ceko investigated the role and location of selenium in the ovary, and a specific protein that includes selenium. The results of her study show how important selenium is to the development of healthy ovarian follicles, which are responsible for the production of eggs in women. 

"Selenium is an essential trace element found in protein-rich foods like red meat, seafood and nuts. It is important for many biological functions, such as immune response, thyroid hormone production, and acts as an antioxidant, helping to detoxify damaging chemicals in the body," Ms Ceko says. 

"We've known for some time that selenium is important to men's fertility, but until now no-one has researched how this element could be involved in healthy reproduction in women." 

Thanks to the use of facilities at the Australian Synchrotron in Victoria, the research team, led by Associate Professor Hugh Harris and Professor Ray Rodgers, was able to pinpoint exactly where selenium is located in the ovary. They then turned their attention to the selenoprotein known as GPX1. 

"Our findings are important, because they show that selenium and selenoproteins are at elevated levels in large, healthy ovarian follicles. We suspect they play a critical role as an antioxidant during the late stages of follicle development, helping to lead to a healthy environment for the egg," Ms Ceko says. 

"We found that gene expression of GPX1 was significantly higher - in some cases double - in egg cells that yielded a pregnancy." 

Selenium deficiency is not usually a problem in Western diets, although people who avoid certain food groups or eat food mainly grown on selenium-deficient soils are at risk. 

"Infertility is a significant problem in our society, with one in six couples in Australia being infertile. Further research is needed to better understand how selenium levels could be optimized, helping to improve women's chances of conceiving. Too much selenium can also be toxic, so it isn't just a case of taking multiple supplements," Ms Ceko says. 

This research, published in the international journal Metallomics, has been supported by the Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC).

 Source:Australian Research Council (ARC) ,National Health and Medical Research Council (NHMRC).