Role of Ayurvedic drug in the form of churna in management of uterine disorder

Phase 2/3

Not yet recruiting

• Conditions: Other specified noninflammatory disorders of uterus. Ayurveda Condition: YONIROGAH/YONI-VYAPADA,

• Registration Number: CTRI/2021/12/038724
• Lead Sponsor: Kahers Shri BMK Ayurveda Mahavidyalaya

Brief Summary

**NEED FOR THE STUDY**

Infertility is defined as a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. (1) In India, the prevalence of infertility problem experienced by women is 8.8%, (2) In the study conducted the incidence of thin endometrium in ovarian stimulation cycles was found to be as high as 38–66%; the incidence of thin endometrium in IVF was between 1% and 2.5%. (3)

Healthy endometrium is one among the important factors of the female reproductive system, playing key roles in the menstrual cycle as well as healthy pregnancy. *Kshetra* is considered as *Garbhashaya* according to Ayurveda. (4) Endometrium is a component of kshetrawhich is also one among the *Garbha sambhav samagri.*(5)

Healthcare experts link the best chances for a healthy, full-term pregnancy to an endometrium that is neither too thin nor too thick. In contemporary science, assisted reproductive technology (ART) are usually recommend for thin endometrium.

Patients who conceive in the setting of a thin endometrium have a significantly increased risk of early pregnancy loss and miscarriage, these patients also have a twofold increase in low birth weight and preterm delivery, as well as a significantly higher risk of intrauterine growth restriction and composite adverse perinatal outcomes. (6)

Putranjeevak beej churna is said to be *Garbhajeevaka*(7)(Which facilitates implantation & helps in sustenance of garbha). Which indeed will give *poshana* to *Garbhashaya* and lead to healthy conception. So, in this area exploration is needed, if only one potent cost-effective drug can serve the purpose of many drugs/formulations in increasing endometrial thickness. With this view the present study is planned to know the efficacy of *Putranjeevak beej churna* in *Vandhyatva* w.s.r to thin endometrium.

 **REVIEW OF LITERATURE**

“ENDO†means (Inner) “METRIUM†means (womb). Endometrial thickness is one of the factors contributing to Female infertility. Endometrial thickness is important in pregnancy.  The physiological functions of the uterine endometrium (uterine lining) are preparation for implantation, maintenance of pregnancy if implantation occurs, and menstruation in the absence of pregnancy. The endometrium thus plays a pivotal role in reproduction. (8)

. This allows the embryo to implant successfully and receive the [nutrition](https://www.medicalnewstoday.com/articles/160774.php "What is nutrition, and why does it matter?") it needs. According to the [Radiological Society of North America (RSNA)](https://pubs.rsna.org/doi/full/10.1148/radiographics.21.6.g01nv211409), the endometrium is at its thinnest during menstruation, when it usually measures between 2–4 millimetres (mm) in thickness. The first half of the proliferative phase starts around day 6 to 14 of a person’s cycle, or the time between the end of one menstrual cycle, when bleeding stops, and before [ovulation](https://www.medicalnewstoday.com/articles/150870.php "Everything you need to know about ovulation"). At this phase, the endometrium begins to thicken and may measures between 5–7 mm.

As the cycle progresses and moves towards ovulation, the endometrium grows thicker. About 14 days into a person’s cycle, hormones trigger the release of an egg. During this [secretory phase](https://www.oatext.com/secretory-phase-of-menstruation-and-implantation.php#Article), endometrial thickness is at its greatest and can reach up to [16 mm](https://pubs.rsna.org/doi/full/10.1148/radiographics.21.6.g01nv211409).(9) It was found that an endometrial lining of less than 8 mm was associated with a significantly higher miscarriage rate . The rate of miscarriage decreased with increasing endometrial thickness >8 mm. (10)

 **DRUG REVIEW**

*Putranjeevaka Beeja Churna*

REFFERANCE:  *Raj Nighantu-( 9/138-139) (11)*

Putranjeevaka is sheeta, Vrushya, Shleshmakara, Garbhajeevaka, Chakshushya, Pittashamak, Daaha-trushna nivarana

**Treatment drug***: putranjeevak beeja churna*

| | | | |

| --- | --- | --- | --- |

|Latin name

Family

Part used

Pharmacological properties

|*Putranjiva roxburghii*

*(Wall)(12) (**a)*

euphorbiaceae

Beeja churna

Aphrodisiac, Beneficial to foetus

| | | | | | | |

| --- | --- | --- | --- | --- | --- | --- |

|***Dravya***

***Rasa***

***Guna***

***Veerya***

***Vipaka***

***Doshaghnata***

***Karma***

|*Putranjeevak*(b)

*Madhura, Katu*

*Guru, Picchila*

*Sheeta*

*Madhura*

*Vata, Pittahara*

*Vrushya, Daha-Trushna hara*

**Control drug****: *Garbhaprad yog***

| | | | |

| --- | --- | --- | --- |

|Latin name

Family

Part used

Pharmacological properties

|Mesua ferrea (13)(a)

Guttiferae

*Pun-keshar*

Stimulant, Tonic, Haemostatic

|Zingiber officinale(b)

Zingiberaceae

*kanda*

Digestive

Gastro-Intestinalstimulant

|Piper longum(c)

Piperaceae

*phala*

Aphrodisiac, Stimulant,

|Piper nigrum(d)

Piperaceae

*phala*

Stimulant

| | | | | | | |

| --- | --- | --- | --- | --- | --- | --- |

|***Dravya***

***Rasa***

***Guna***

***Virya***

***Vipak***

***Doshaghnata***

***Karma***

|*Nagakeshar*

*Kashay,*

*Tikta*

*Rukshya,*

*Laghu*

*Ushna*

*Katu*

*Kapha*

*Pitta*

*Shamak*

*Pachana*

*Kandughna*

*Dourgandhya*

*Hara*

|*Sunthi*

*Katu*

*Laghu*

*Snigdha*

*Ushna*

*Madhura*

*Vatahara*

*Pachana*

*Vrushya*

*Bedana*

|*Pippali*

*Katu*

*Tikshna*

*Laghu*

*Snighdha*

*Anushna*

*Madhura*

*Kaphavata*

*Shamaka*

*Dipana*

*Pachana*

*Vrushya*

*Rechaka*

|*Marich*

*Katu*

*Tikshna*

*Ushna*

*Katu*

*Kaphavata*

*Shamaka*

*Dipana*

*Chedhana*

*Avrushya*

**Previous Works Done**

Dr. Riddhi Acharya et.al. 2018, Evaluated that Garbhaprad Yog is significant in managing Thin endometrium in infertile females at the dose of 6gms OD when given for 60 days. (14)

Dr. Swarda Uppin et.al.  2016, Evaluated that Roupyadi bhasma was effective in improving endometrium thickness in infertile females at the dose of 202.5mg BD for 3 days. (15)

Rajurkar et.al. 2018, Studied that Putranjiva roxburghii in the form of herbal medicated feed was effective in increasing progesterone and increased fecundity percentage in wistar rats when administered for a period of 63 days. (16)

Acharya Balkrishna et.al. 2021, Experimented that Supercritical Fluid Extract of Putranjiva roxburghii Wall. was effective in reversing impaired Fertility Impairment in a Zebrafish Model when given for the period of 14 days. (17)

 **AIM:**To study the effect of *EkaMulika* *prayoga* in female infertility.

**OBJECTIVES:**

To evaluate the efficacy of *Putranjeevak beeja Churna* in thin endometrium.

To evaluate the efficacy of *putranjeevak beeja churna* in ovulation.

To compare the efficacy of *Garbhaprad yog* with *Putranjeevak Churna* in thin endometrium.

**HYPOTHESIS**

H0– Efficacy of *Putranjeevak churna* is comparable with Garbhaprada yoga *in* the management of *vandhyatva.*

H1 - Efficacy of *Putranjeevak churna* is not comparable with Garbhaprada yoga *in* the management of *vandhyatva.*

**RESEARCH** **QUESTION**

Whether the administration of *Putrajeevak Churna* in the dosage of 6gms BD for 60 days is effective in management of V*andhyatva* w.s.r to thin endometrium?

**MATERIALS AND METHODOLOGY**

**Materials**

**Literary source**

The source of data study will be taken from library, classical text, modern textbooks, Relevant research articles and internet.

**Drug source**

Drug will be prepared in GMP certified KLE Ayurveda pharmacy.

**Clinical study:**

Patients will be taken from OPD and IPD section of Srishti Fertility centre, Department of Prasuti Tantra & Stree Roga, KLE Ayurveda Hospital and Medical Research Centre, Belagavi.

**METHODOLOGY**

**RESEARCH DRUG**:

**Control Group: *Garbhaprad yog***

**Trial Group:   *Putranjeevaka beeja churna***

**Authentication****:**

Authentication of raw drugs will be obtained from Central Research Facility, AYUSH approved Drug testing laboratory for ASU drugs, KAHER’s Shri BMK Ayurveda Mahavidyalaya & Post Graduate Studies and Research Centre, Belagavi.

**Drug procurement**

Raw materials of Trial drug and Control drug will be procured from GMP certified pharmacy

**Drug preparation**

Trial drug and Control drug will be prepared in GMP certified KLE Ayurveda pharmacy, Belagavi.

**Packaging and storage**

The drugs for Control and trial group will be packed and stored under standard storing conditions at MRC, KLE Ayurveda Hospital and Medical Research Centre, Belagavi.

**MAIN STUDY**CLINICAL STUDY

**STUDY TYPE**  INTERVENTIONAL

**STUDY DESIGN**   RANDOMISED CONTROL CLINICAL TRIAL

**MASKING**  Open Label

**CONTROL** Controlled

**GROUP** 2 Groups

**SAMPLE SIZE**  20

**Groups and intervention:**

| | | | | |

| --- | --- | --- | --- | --- |

|**NAME OF THE GROUP**

**SAMPLE SIZE**

**INTERVENTION WITH DOSE**

**DURATION**

***ANUPANA***

|GROUP- controlled

10

Garbhaprad yoga

6 gms OD

     60 days

Ghee

|GROUP- Trial

10

Putranjeevaka beeja churna

6 gms BD

60 Days

Ghee

 **Visits and follow-up**

| | | |

| --- | --- | --- |

|VISIT

DAY

ASSESSMENT

|1.

Day 0

·        Screening

|2.

Day 12th /14th /16th of

Same menstrual cycle

 Â·        Screening of Endometrial thickness & Ovulation assessment by TVS

·        Enrolment

|3.

Day 3rd of nextmenstrual cycle

Ø Drug intervention

|4.

Day 12th

Day 12th/14th/16th of the same menstrual cycle

Ø Endometrial thickness

Ø Ovulation assessment by TVS

|5.

5th day of second menstrual cycle

Ø Assessment of subjective parameters

|6.

Day 12th

Day 12th /14th /16th day of the second menstrua cycle

Ø Endometrial thickness. Ovulation assessment by TVS

|7.

5th day of third of menstrual cycle

Assessment of subjective parameters

**DIAGNOSTIC CRITERIA****:**

Endometrial thickness (< 8mm) by TVS on day 12th menstrual cycle

 **Inclusion criteria**

Infertile female patients between the age group 20 to 40 yrs.

Sonographically diagnosed cases of Endometrial thickness < 8 mm.

Patients having Regular menstruation.

**Exclusion criteria**

k/c/o uterine growths, fibroids and malignancy.

k/c/o Venereal diseases

k/c/o congenital abnormality of reproductive system.

**Withdrawal Criteria’s**

The Principal Investigator may stop the participation of subject from the study at any time for one or more of the following reasons.

Any serious adverse events requiring major interventions.

Any time during the study continuation of study drug could lead to harmful effect.

Subjects’ failure to follow the instructions of the Principal Investigator.

If patients need treatment that are not allowed in the study.

If patient want to discontinue with the medication.

If patient gets pregnant.

 **RESCUE MEDICATION**

Any of the manifestations or adverse drug reactions will be managed with the appropriate measures. Serious complications if any developed will be referred to tertiary care centre.

**STUDY SITE:**KLE Ayurveda Hospital and Medical Research Centre Shahapur, Belagavi.

**STUDY PERIOD:**18 months

**End point**: Increase in endometrial thickness

After approval of ethical clearance, all subjects will be randomised into group with method of randomisation and will begin the study.

**ASSESSMENT CRITERIA**

**Objective Parameters**

Trans-vaginal-sonography:

ET on 12th day of menstrual cycle

Ovulation on day 12th /14th /16th menstrual cycle

**Subjective Parameters**

Duration of bleeding

Interval between two cycles

Number of pads used per cycle

Dysmenorrhea

Clots

**Expected Outcome**

Putranjeevak beeja churna will be effective in the management of  Thin  Endometrium.

**Statistical**

Parametric test  Between groups - Independent sample t test

Within group - paired t test

Non parametric  Between groups - Mann-Whitney

Within group – Wilcoxon

DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTION CONDUCTED ON ANIMALS, PATIENTS OR HUMAN?

HAS THE ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION?  YES

ETHICAL CLEARENCE NUMBER – BMK/20/PG/RV/6

**CTRI NO.****-** Yet to be registered

**Bibliography**

**1**World Health Organization (WHO). International Classification of Diseases, 11th Revision (ICD-11) Geneva: WHO 2018.

**2**  Dhair A, Abed Y. The association of types, intensities and frequencies of physical activity with primary infertility among females in Gaza Strip, Palestine: A case-control study, 2020;15(10).

**3** Kimberly E. Liu1, Hartman M, Hartman A., Management of thin endometrium in assisted reproduction, ELSEVIER 2019 jul, 39(1), Pg 49-62

**4** Shastri K A,Shushrut Samhita of sushrut sharir sthana 5/51(1),Varanasi chaukhamba ,Sanskrit santhana, Reprint 2016;64.

**5** Tiwari p, Ayurvediya Prasuti-Tantra Evam Stri-Roga 2, 2nd Edition, Varanasi, Chaukhamba Orientalia, Reprint 2012;275.

**6** Mouhayar Y, Franasiak JM, Sharara FI. Obstetrical complications of thin endometrium in assisted reproductive technologies: a systematic review. J Assist Reprod Genet. 2019 Apr;36(4):607-611.

**7**  Dr. Satish chandra Sankhyadhar, Dr. Deepika Sankhyadhar , Raj Nighantu ,2017, Chaukhamba Orientalia , Varanasi, prabhadradi varga 9/138-139 pg.465-467.

**8** Critchley HOD, Maybin JA, Armstrong GM, Williams ARW. Physiology of the Endometrium and Regulation of Menstruation. Physiol Rev. 2020 Jul 1;100(3):1149-1179.

**9** [Kenneth M. Nalaboff](https://pubs.rsna.org/author/Nalaboff%2C+Kenneth+M "Kenneth M. Nalaboff"), [John S. Pellerito](https://pubs.rsna.org/author/Pellerito%2C+John+S "John S. Pellerito"), [Eran Ben-Levi](https://pubs.rsna.org/author/Ben-Levi%2C+Eran "Eran Ben-Levi"), Imaging the Endometrium: Disease    and Normal Variants, [Radiological Society of North America (RSNA)](https://pubs.rsna.org/doi/full/10.1148/radiographics.21.6.g01nv211409)Nov 1 2001, [Vol. 21, No. 6](https://pubs.rsna.org/toc/radiographics/21/6), 1409-1423

**10** Mouhayar Y, Franasiak JM, Sharara FI. Obstetrical complications of thin endometrium in assisted reproductive technologies: a systematic review. J Assist Reprod Genet. 2019 Apr;36(4):607-611.

**11** Dr. Satish chandra Sankhyadhar, Dr. Deepika Sankhyadhar , Raj Nighantu ,2017, Chaukhamba Orientalia , Varanasi, prabhadradi varga 9/138-139 pg.465-467.

**12** Prof Sharma pv, *Dravya Guna Vijnana*, 12th ed. Varanasi: Chaukhambha Orientalia; 1991 Pg. no. 590-592.

**13** Hegde P.,Harini A., Dravyagun Vidnyana, vol 2,2016,chaukhamba publications, Varanasi

**14** Acharya R. & Patil M., APilot Study of Efficacy of Garbhaprad Yog in Endometrial Thickness. International Ayurvedic Medical Journal, 2018 ,6(5), pg 974-976

**15** Uppin S., an exploratory study to evaluate the kshetra vishodhan effect of roupyadi bhasma in female infertility w.s.r to endometrial thickness, submitted KAHER’S Shri BMK Ayurvedic Mahavidyalaya and Research centre,2019.

**16** Rajurkar SS., Jadhav ND, Ballurkar BV, Rajurkar SR, *Putranjiva roxburghii*: Medicated feed as uterine tonic in wistar rats, International Journal of Veterinary Sciences and Animal Husbandry 2018; 3(5): 16-22.

**17** Balkrishna A, Nain P, Joshi M, Khandrika L, Varshney A. Supercritical Fluid Extract of Putranjiva roxburghii Wall. Seeds Mitigates Fertility Impairment in a Zebrafish Model. Molecules [Internet]. MDPI AG; 2021 Feb 15;26(4):1020.

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2021-06-11
• Study Start: 2022-01-01

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

Infertile female patients between the age group 20 to 40 yrs Sonographically diagnosed cases of Endometrial thickness < 8 mm Patients having Regular menstruation.

Exclusion Criteria

k/c/o uterine growths, fibroids and malignancy k/c/o Venereal diseases k/c/o congenital abnormality of reproductive system.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Trans-vaginal sonography	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
ET on 12th day of Menstrual cycle	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Ovulation on day 12th 14th 16th of Menstrual cycle	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Subjective Parameters	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Duration of bleeding	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Interval between two cycles	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Number of pads used per cycle	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Dysmenorrhea	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots
Clots	Objective | Trans-vaginal sonography | ET on 12th day of Menstrual cycle | Ovulation on day 12th 14th 16th of Menstrual cycle | Subjective Parameters | Duration of bleeding | Interval between two cycles | Number of pads used per cycle | Dysmenorrhea | Clots

Trial Locations

Locations (1)

Kahers shri BMK Ayurvedic mahavidyalaya; 🇮🇳 Belgaum, KARNATAKA, India

Kahers shri BMK Ayurvedic mahavidyalaya

🇮🇳Belgaum, KARNATAKA, India

Dr Kashvva V Hiremath

Principal investigator

9448945687

drkvhiremath@gmail.com