MANAGEMENT OF FEMALE INFERTILITY W.S.R. TO ANOVULATION WITH UNANI FORMULATION-CASE SERIES. Kafeel Ghazia and Shameem Ismath

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Rise in number of infertile couple is a major concern worldwide. More and more number of male and female are prone to infertility in cities due to life style. Anovulation is responsible for 30-40% of infertility. It is recommended that the administration of ovulation inducing agents be carried out only when they are indicated in order to achieve pregnancy rates without increase in untoward side effects. The first line of treatment in conventional medicine for induction of ovulation is use ofovulation inducing drugs. However, therapy may cause side effects like increased risk of ovarian hyperstimulation, abortion, multiple pregnancies etc and are contraindicated in liver dysfunction, breast diseases, h/o severe side effects etc; hence this treatment may not be suitable in all cases. Therefore, the number of couples turning to technologies and artificial methods like IVF (In Vitro Fertilization) is increasing. Due to the high cost of ART procedures, it is beyond the reach of some patients hence finding an alternative therapy has been always in the need. In classical unani literature, various formulations has been mentioned for the treatment of uqr, possessing the properties like muqawwi rehm, moaene hamal, moallide mani which are to be used from the 5th day of menstrual cycle (corresponds to ovulation inducing drugs) as conception is most likely to take place after menstruation. Such types of drugs are known to contain phytoestrogens and may induce ovulation by maintaining hormonal balance therefore present case study has been done by using hab hamal (unani medicine ) in anovulatory patients.

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Ovulation is the central event in female reproduction . 1 Coordinated effects of hypothalamic gonadotropin releasing hormones, pituitary gonadotropins, ovarian estrogens and follicular response to these effects result in ovulation. Any derangement of the above factors results in ovarian dysfunction. 2 Today nearly 30-40% of infertile patients suffer from ovulatory dysfunction 2 in which 75% have polycystic ovaries and 20 to 25% of women with normal ovulation; demonstrate ultrasound findings typical of polycystic ovaries. 3 Anovulation can be a feature of hypothalamic anovulation, hyperprolactinaemia, polycystic ovaries, luetinised unruptured follicles and luteal phase deficiency. 2 In majority of these women, the disorder of ovulation is obvious because there is a complete lack of menstruation (primary or secondary amenorrhoea) or infrequent menstruation (oligomenorrhoea) Therefore the exact prediction of ovulation is important in many infertile women. Until recently, treatment was largely empirical and resulted in disappointing conception rates, but a diagnosis with accurate therapeutic implications can now be reached in most ISSN: 2320-5407 Int. J. Adv. Res. 5(6), 277-282 278 patients. 4 The availability of drugs to induce ovulation has been one of the most significant advances in the treatment of infertility in the past 25 years. 3 As neuroendocrinology and ovarian physiology has advanced, new ways of restoring normal physiology with the induction of ovulation have appeared and thus, the choice of the correct agent for the induction of ovulation is dependent upon a specific diagnosis. Until recently, treatment was largely empirical and resulted in disappointing conception rates, but a diagnosis with accurate therapeutic implications can now be reached in most patients. 4 Of all the infertility factor, disorder of ovulation has the widest range of treatment armamentarium. It is recommended that the administration of ovulation inducing agents be carried out only when they are indicated in order to achieve pregnancy rates without increase in untoward side effects. 5 The first line of treatment in conventional medicine for induction of ovulation is use of clomiphene citrate therapy for 5 days after menstruation. However, clomiphene citrate therapy may cause side effects like increased risk of ovarian hyperstimulation, abortion, multiple pregnancies etc and are contraindicated in liver dysfunction, breast diseases, h/o severe side effects etc. There has been a broad description of infertility in unani system of medicine also. In classical unani literature infertility has been mentioned centuries back and defined as when conception fails to occur or when there is a difficulty in conception either due to the defect in male or female partner. Defect in female partner are attributed to the diseases of ovaries (aazae mani), uterus (rehm) or idiopathic. There are various causes of female infertility as mentioned in unani literature. According to Unani physicians, if the cause of infertility is in female gamete (ovum), it is either due to qillate maddae manwia (anovulation) or fasaad mani (dysovulation).The defect in ovum is attributed to sue mizaj barid which solidifies the mani leading to infertility. 6,7,8,9,10 Hippocrates has mentioned that defect can occur in both male mani (sperm) and female mani (ovum). 7,8,9, Other causes of female inferiltiy includes defects in ovaries like warm khusiyatur rehm (oophoritis) 10 , menstrual irregularities 14,15,16 , defects in uterus like metritis , inversion of uterus , prolapse of uterus (Warm rehm, Mailan rehm , Inqalabur rehm ) and Congenital defects of uterus . General causes include obesity (samne mufarrat ) disease of other organs (Aaze shareefa wa rayeesa) such as disorders of nervous system and brain (Zoaf dimagh ), cardio vascular system (Zoaf qalb) , liver disorders (Zoaf jigar) , anxiety and stress (Khouf , Gham) anaemia( Sou ul quniya) 6,7,8,9,10,11,12,13,14,15,16,17,18,19 . In classical unani literature, various formulations has been mentioned for the treatment of anovulatory infertility, possessing the properties like uterine tonic (muqawwi rehm), moaene hamal, ovulation inducing drugs (moallide mani) which are to be used from the 5th day of menstrual cycle (corresponds to ovulation inducing drugs). 6,7,20 Such types of drugs are known to contain phytoestrogens and may induce ovulation by maintaining hormonal balance. 13 Unani formulation may induce ovulation by ovulation (increasing maddae manwia) and result in conception as it is helpful in conception (moaene hamal): hence beneficial in cases of anovulatory infertility. 11,12,13,14,15,16,17,18,19,20 The main objective of the study is to explore the efficacy of unani formulation scientifically for treatment of anovulation.

Case History 1:-
A 23 year old female, registration no 00436, visited the OPD of National Institute of Unani Medicine, Hospital , Bangalore nium hospital with history of primary infertility since 3 years for the first time on 15/10/2009 . She had infrequent menstrual cycles occurring at 2-3 months only on induction with moderate flow. General examination reveals moderate hirsuitism, mild acne, acanthosis nigricans was also present. Husband Semen Analysis: shows normal sperm count and motility Treatment:-Treatment was initiated with the compound formulation hab hamal 1 tab twice daily with milk from the second day of next menstrual cycle with LMP-14/02/2011 for 5 days along with this majoon supari pak 7 gm twice daily.

Results:-
Patient came on 30/03/2011 with 45 days amenorrhoea. Urine pregnancy test was conducted at hospital and found positive. Pregnancy continued till term and delivered a healthy baby.

Case History 5:-
A 28 year old female Mrs SB with OPD registration no 005071 visited the OPD of National Institute of Unani Medicine, Hospital , Bangalore hospital for the first time on 9/05/2011. She complains of not able to conceive since 5 years. She had regular menstrual cycle of 24-25 days but with scanty flow since one and half years with LMP-07/05/2011.There was no h/o diabetes mellitus, hypertension or any chronic illness like Koch disease. Married life was of 5 years. General examination reveals no hirsuitism, no acne, no acanthosis nigricans. Per speculum shows no vaginitis, cervix was healthy and External os was Nulliparous P/V -Uterus -Anteverted , Normal Size , Fornices Free , firm and mobile .

Investigations-
Baseline investigations such as Complete blood picture with ESR, random blood sugar, lipid profile, VDRL, HIV I and II and urine examination were normal . Patient was further evaluated for the patency of fallopian tubes. Patient was advised hormonal profile on the second day of next menstrual cycle in the fasting and HSG on 9 th day in the same menstrual cycle .Hormonal profile include S.FSH, S.LH, Thyrid profile and S. prolactin were in the normal limits.Patient had follicular study done on 19/3/11 which reveals unruptured dominant follicle of 26*22mm with POD free which were suggestive of anovulatory cycles.
HSG -both fallopian tubes were patent with normal shape size and position of uterus Husband Semen Analysis: shows normal sperm count and motility Treatment:-After required investigations the patient was diagnosed with anovulatory cycle and treatment was initiated with the compound formulation habbe hamal 1 tab twice daily with milk from the second day of next menstrual cycle for 5 days along with this majoon supari pak 7gm twice daily.
Patient came with H/O missed period with lethargic feeling on 15/07/2011. Urine pregnancy test was conducted at hospital and found positive. Patient took proper antenatal care and delivered female child full term.

Discussion:-
Hab hamal was found to be effective in the treatment of anovulatory infertility. Effect of habbe hamal can be attributed to the constituents present in this compound formulation. 20 21 Macelignan is a natural compound isolated from M. fragrans. It enhanced the insulin sensitivity and improved lipid metabolic disorders by activating peroxisome proliferator receptor (PPAR, á/ã) and attenuating endoplasmic reticulum stress, suggesting that it is an antidiabetic agent for the treatment of type 2 diabetes (Han et al., 2008) 22 In Unani medicine, M. fragrans (nutmeg) has been mentioned to be of value in the management of male and female sexual disorders. In an experimental study, Tajuddin et al. (2005) have found that the oral administration of 50% ethanolic extract of nutmeg at 500 mg/kg body weight produces a significant and sustained increase in the sexual activity of normal male rats without any conspicuous adverse effects, which might be attributed to its nervous stimulating property. 22 In a study conducted by Mokhtari et al have found that hydro-alcoholic saffron extract can promote the pituitary-ovary axis activities at all levels, cause an elevation in the serum concentrations of LH, FSH and estradiol hormones, as well as increase the mean numbers of secondary follicles and eventually ovarian weight. It is probable that these effects are the results of active compounds such as crocin, crocetin and saffranal, all of which are present in the extract. 23 It can be suggested that one might use saffron to enhance fertility and treat infertility in females, although further studies are still required which is in accordance with the therapeutic effects mentioned in unani literature.

Conclusion:-
Hab hamal has been mentioned in the classical unani literature for the treatment of infertility. Based upon the above case studies, it is further recommended to have a clinical trial on a larger sample size in order to prove its efficacy in treatment of anovulatory infertility scientifically.