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 kshetra which 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 it needs. According to the Radiological Society of North America (RSNA), 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. 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, endometrial thickness is at its greatest and can reach up to 16 mm.⁽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

Control drug: Garbhaprad yog

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 Vandhyatva 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:

Visits and follow-up

DIAGNOSTIC CRITERIA:

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

Ovulation on day 12^th /14^th /16^th 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, 2^nd 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, John S. Pellerito, Eran Ben-Levi, Imaging the Endometrium: Disease    and Normal Variants, Radiological Society of North America (RSNA)Nov 1 2001, Vol. 21, No. 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.