In clinical medicine, secondary infertility is defined as an inability to conceive despite exposure to pregnancy for one year (2 years in some epidemiological studies), after having conceived at least once previously. In countries with limited resources, secondary infertility is a prevalent, curable, and unaddressed reproductive health issue. Following a year of unsuccessful attempts at conception, the couple is typically referred for evaluation. But it is well known that primary infertility is much more frequent than secondary infertility in resource-rich nations, whereas the opposite is true in sub-Saharan Africa (Dhont N, 2011). Evidence suggests that male factors contribute to 30% of infertility, female factors to 45%, and unidentified causes account for 25% of cases (Kazemeini SK, 2017). With a prevalence rate ranging from 8% to 37%, this type of infertility is known as "unexplained infertility"(Kamath MS, 2016). The fundamental assessment of infertility should take into account signs of ovulation, the condition of the fallopian tubes, and adequate sperm production Kamath MS, 2016). On the basis of the common tests carried out during the evaluation of infertility, the recommended treatment options frequently depend on the etiology. Some factors, such as expectant management, can be taken into account in young women (25 years), especially if the duration of infertility is less than 3 years, which is not applicable in older women (>35 years) (Kazemeini SK, 2017). The like hood of becoming pregnant is decreased by 2%, or roughly 25%, for every additional month of infertility beyond the average (Kamath MS, 2016).

Numerous plants and plant-based products have been shown in the Unani System of Medicine to effectively treat stress, impotence, and infertility (Ahmad MK, 2010). As conception is most likely to occur after menstruation, a number of formulations with the properties of muqawwi bah (Aphrodisiac), muqawwi rahim (Uterotonic), muwallid-i-mani (ovulation-inducing), and mughalliz-i-mani (an agent which increases the viscosity of semen) have been mentioned for the treatment of infertility (Shameem I, 2019; Khan MA, 2003; Majoosi AIA, 2010; Begum S, 2020; Sina I, 2010; Ghani N, 2011) and are to be used starting from the fifth day of the menstrual cycle. These medicines are known to contain phytoestrogens and may cause ovulation by keeping the hormonal balance in check (Shameem I, 2019). We present a case of secondary infertility without apparent cause in which the impact of an Unani formulation was investigated.

A married couple (28-year-old female and 29-year-old male partners) with a history of secondary infertility issues was referred to the gynecology OPD at NIUM Hospital. The couple has been trying to conceive for the past 1.5 years after getting married. The couple has been trying to conceive for the past 1.5 years after getting married, and they report feeling extremely stressed out because of their lack of success. The patient reported a regular menstrual cycle of 28-30 days with a moderate amount of flow for 3-4 days her BMI was 26.93 kg/m2, and she attained menarche at 12 years of age. The patient never had menstrual molimina or headache, visual disturbances, galactorrhea, vasomotor symptoms, or reduction in exercise tolerance with no significant medical or surgical history. The couple reported consanguinity in marriage but there was no family history of infertility on either side of the partner. The patient was a housewife, did not smoke, drink alcohol, or use any other drugs, and is from a low socioeconomic group. In addition to being in good health, the patient's partner reported no issues with erection, ejaculation, or pain during sexual activity. He had no significant medical or surgical history and never had urogenital infections or been exposed to STDs. He is a vegetable vendor by trade and does not smoke, drink excessively, use drugs, or self-medicate. Three to four times a week, the couple engaged in vaginal intercourse.

The woman had no successful pregnancy outcome, as she had a history of spontaneous abortion at 5 months of gestation due to premature membrane rupture in her first pregnancy three years prior, followed by the history of stillbirth at the hospital at 8 months of gestation in her second pregnancy 1.5 years prior.

Her vital signs were stable, and a systemic examination revealed nothing abnormal. A per vaginal examination revealed a firm, mobile, normal-sized, anteverted uterus without fornicial tenderness. The investigation was recommended, and the male partner's semen analysis revealed a 50 million sperm study with normal morphology and good motility. She had a B-positive blood group, Hb percent of 10.7mg/dl, FBS of 73mg/dl, TSH of 1.31mU/L, and normal CUE when her CBC, ABO Rh typing, CUE, and FBS results were obtained.

The Unani compound formulation consists of Majoon Mocharas 5gm, Sharbat Unnab 20ml, Jawarish Amla 5g, which was taken twice daily, and 6g powder of Baikh asgand (Withania somnifera Dunal), Baikh piyabansa (Barleria prionitis Linn), Gule dhawa (Anogeissus latifolia), and Gule nilofar (Nymphaea alba Linn), taken with milk for 5 days starting from the fifth day of last menstrual period. In addition, the patient was advised to have timed intercourse.

Asgand contains alkaloids and steroidal lactones as main constituents, gul dhawa consists of saponins, tannin quercetin, and phenolic compounds, gule nilofar is rich in alkaloids, whereas piyabansa contain anthraquinone pigmented, barleriaquinone; all these constituents are responsible for phytoandrogen-oogenic, antistress and insulin-sensitizing activities (Shameem I, 2019; Anonymous, 2003; Gupta AK, 2004; Satyavati GV, 1987).

The description of the single drug is given as follows:

Fig. 3 Baikh Asgand (Withania somnifera Dunal)

It is a well-known Unani medicine used in many parts of the world. It is also known as Indian ginseng, has been described in Unani medicine as muwallid-i-Mani (ovulation-inducing), and mughalliz-i-mani (an agent which increases the viscosity of semen), muqawwi Rahim. A mixture of powder of asgand 1 part, ghee 1 part, and milk 8th or 10th part is very effective for conception if taken soon after menstruation. Asgand is beneficial in gynecology for irregular menstruation, female and male infertility, and impotence.

Fig. 4 Baikh piyabansa (Barleria prionitis Linn)

It is a tropical Indian plant, used as a medicine for a long time. It possesses emmenagogue, analgesic, appetizer, hemostatic and antiseptic properties and is beneficial for conception when used in a dose of 10.5 g with milk.

Fig. 5 Gule dhawa (Anogeissus latifolia)

The tree is remarkable for the large amount of gum that flows from it, hence known as Dhawa. Flowers are used as an aphrodisiac, astringent, antipyretic, refrigerant, anthelminthic and antidiarrheal.

Fig. 6 Gule nilofar (Nymphaea alba Linn)

Flowers have androgenic and reproductive properties. It is a well-known Unani medicine used for thousands of years by eminent Unani physicians and described by Ibn Sina in his book “advia qalbia” as a potent mufarrah (tranquilizer). It possesses aphrodisiac uterotonic and anti-inflammatory properties and is useful in impotency, premature ejaculation, etc.

During follow up it was observed that the patient had a response to the treatment i.e.; after taking the Unani compound formulation for just one cycle. She missed her period and urine for pregnancy test revealed that she was pregnant, and an early obstetric scan revealed an early intrauterine gestation of 6 weeks 3 days, with evidence of cardiac activity.

A couple is typically referred for evaluation in the OPD of the National Institute of Unani medicine Bangalore after 1.5 years of unsuccessful attempts at conception. The couple had no successful pregnancy outcome, as she had a history of spontaneous abortion at 5 months of gestation due to premature membrane rupture in her first pregnancy three years prior, followed by the history of stillbirth at the hospital at 8 months of gestation in her second pregnancy 1.5 years prior, suggested secondary infertility. Her vital signs were stable, and a systemic examination revealed nothing abnormal. A per vaginal examination revealed a firm, mobile, normal-sized, anteverted uterus without fornicial tenderness with a regular menstrual cycle of 28-30 days with moderate flow. The investigation was recommended for both the partners, and the male partner's semen analysis revealed a 50 million sperm study with normal morphology and good motility. Despite being consanguineous in marriage, neither partner's side of the family had a history of infertility, as parental consanguinity has been linked to stillbirths, low birth weight, preterm delivery, abortion, infant and child mortality, congenital birth defects, cognitive impairments, cardiovascular risks, malformations, and many other complex disorders.

In young women (25 years), expectant management can be considered, especially if the duration of infertility is 3 years, which is not applicable in the advanced age of women (>35 years). Treatment decision is based on prognostic factors such as duration of infertility and age of the female partner (Kazemeini SK, 2017). The likelihood of becoming pregnant is decreased by 2%, or roughly 25%, for every extra month of infertility (Shameem I,2019). The patient, in this case, was 28 years old, but she was unable to become pregnant despite 1.5 years of unprotected sexual activity and after receiving modern treatment, which caused the couple stress and demonstrated the need for conventional treatment.

Numerous formulations have been offered for the treatment of infertility in the Unani system of medicine, and one of the most successful formulations has been used to help a stressed-out couple conceive. The ingredient combination includes Baikh asgand (Withania somnifera Dunal), Baikh piyabansa (Barleria prionitis Linn), Gule dhawa (Anogeissus latifolia), and Gule Nilofar, which has been mentioned in the Unani system of medicine as having aphrodisiac, uterotonic, ovulation-inducing, phytoandrogen-oogenic, antistress and insulin-sensitizing properties. Since the patient was instructed to take this formulation with milk for five days starting on the fifth day of the previous period and timed sexual activity, fortunately, women conceived within a single cycle.

Unani medicine assisted the patient in becoming pregnant after just one cycle of treatment without producing any observable side effects, and it may be a helpful complementary treatment option in the event that conventional treatments for female infertility are unsuccessful. As a result, this strategy can be taken into consideration when treating stressed-out infertile couples. However, there are still not enough clinical studies on effective Unani formulations. To determine the efficacy of Unani medicines in such circumstances, additional comparative studies utilizing serial follicular monitoring and mid-luteal serum progesterone may be beneficial.

OPD:

Outpatient Department