Protocol of Thesis

Comparison of Clomiphene Citrate & Letrozole for Ovulation Induction in

Polycystic Ovarian Syndrome

For Approval of Subject

Of
Thesis For DNB (Obstetrics & Gynaecology)

Department Of Obstetrics & Gynaecology,

Government Multispeciality Hospital
Sector-16, Chandigarh

BY

DR KHYATI J. PARMAR
NAME OF CANDIDATE : DR KHYATI J. PARMAR

Father's Name : Mr. JAYANT K PARMAR

Address of Candidate : Department Of Obstetrics & Gynecology, Chandigarh

University from which Graduated : VEER NARMAD SOUTH GUJARAT

Date of joining DNB course : 30/8/2023

Proposed subject of Thesis : " Comparison of Clomiphene Citrate & Letrozole for
Ovulation Induction in Polycystic Ovarian Syndrome".

Facilities for the work on subject : GMSH Sector-16, Chandigarh

 CERTIFICATE OF GUIDES

This is to certify that facilities for work in the subject of thesis exist in this institute and will be

provided to the candidate. We will guide the candidate in her work and see that the data being

included in the thesis is genuine and work is done by the candidate herself. To the best of our

knowledge, no work has been done on this topic in this institute.

Guide : DR BIRINDERJIT KAUR

Department of Obstetrics &
Gynaecology GMSH-16, Chandigarh.

Co- guides : Dr. GUNCHOO KUNDI

Department of Obstetrics Gynaecology
GMSH-16, Chandigarh.

DR HARNEET SANDHU .
M.D,.RADIODIAGNOSIS
Department of Radiology
GMSH -16 ,Chandigarh.

Head of the department: Dr. Birinderjit Kaur (SMO)

Department of Obstetrics &
Gynaecology GMSH- 16, Chandigarh.

DNB Coordinator: Dr. V K Nagpal

Medical Superintendent

GMSH-16, Chandigarh.
 DECLARATION BY THE CANDIDATE

I, Dr. KHYATI J PARMAR Secondary DNB candidate in Department of Obstetrics and

Gynaecology in GMSH -16 Chandigarh, will conduct my thesis entitled" Comparison
of Clomiphene Citrate & Letrozole for Ovulation Induction in
Polycystic Ovarian Syndrome" under the guidance of Dr BIRINDERJIT KAUR
Medica , Department of Obstetrics and Gynaecology, Govt. Multi- Speciality Hospital,
Chandigarh, Dr. GUNCHOO KUNDI (Co-Guide) , Department of Obstetrics and
Gynaecology, DR. HARNEET SANDHU(co guide ) Department of Radiology , Govt.
Multi-Speciality Hospital, Chandigarh.

Place: Chandigarh Dr. KHYATI J PARMAR

Date: Govt. Multi-Speciality, Hospital

Sector-16, Chandigarh.
 INDEX

SR NO CONTENT PAGE NO

1 Introduction 6-7

2 Review of Literature 8-11

3 Aim and Objectives 12

4 Material and Methods 13-17

5 Statistical Analysis 18

6 Ethical justification 18

7 Patient information sheet 19-21

8 Patient informed consent 22-24

9. Perfoma 25-27

10. References 28-29

11 Annexures 30

5
 INTRODUCTION

Polycystic ovary syndrome (PCOS), or Stein-Leventhal syndrome, is a common endocrine

disorder that affects 5-10% of women in reproductive age group. PCOS accounts for the vast
majority of anovulatory symptoms and hyperandrogenism in women, especially in a younger
age.2 PCOS when diagnosed has life-long implications on the individual, with increased risk
for infertility, metabolic syndrome, and type 2 diabetes mellitus and possibly for cardiovascular
disease and endometrial carcinoma in the later stage of life.

The cause of PCOS is not clearly understood. Considerable evidence suggests that it arises
as a complex trait with contributions from both heritable and nonheritable intrauterine and
extrauterine factors, among which insulin resistance and obesity are most common factor
responsible.6,7 Usually, functional ovarian hyperandrogenism is considered the major source of
the androgen excess8-10 and can account for the major features of the syndrome including
hirsutism, anovulation, and polycystic ovaries.8,11 This ovarian dysfunction is unique as it
appears to be intrinsic and is characterized by abnormal ovarian steroidogenesis12 and
folliculogenesis. that are manifested clinically by anovulation and androgen excess.

Clomiphene citrate, a selective estrogen receptor modulator, has been used for
ovulation induction since the 1960s. It has been considered to be first-line therapy for women
with PCOS. However, some women do not ovulate with clomiphene citrate, some experience
adverse antiestrogenic endometrial effects, and there is an increased risk of multiple gestation
(twins 6 to 9 percent, triplet pregnancies are rare). Women with PCOS often have anovulatory
infertility. Clomiphene citrate is the most commonly used pharmacologic agent to induce
ovulation in these women, but some women fail to conceive with this therapy. During the past
decade, aromatase inhibitors have been explored as an option for ovulation induction in women
who fail to conceive with clomiphene citrate. Aromatase inhibitors are a class of drugs that
block estrogen biosynthesis, thereby reducing negative estrogenic feedback at the pituitary.
Aromatase inhibitors are widely used as adjuvant endocrine therapy for postmenopausal
women with breast cancer.Nowadays,letrozole has been extensively used in ovulation
induction in anovulatory infertility &to augment follicles for ovulatory women.25They have
been used in the treatment of patients with anovulatory infertility,13 such as PCOS, and for
increasing the number of ovarian follicles recruited in ovulatory women undergoing controlled
ovarian hyperstimulation (COH). 14,15 Available data suggest that letrozole is superior to
clomiphene citrate for the outcome of live birth rates in oligo-ovulatory women with PCOS.16,17

6
Early data suggested that clomiphene and letrozole resulted in similar ovulatory and pregnancy
rates.18,19

This study seeks to address this gap in knowledge by conducting a comprehensive and
comparative analysis of clomiphene citrate and letrozole for ovulation induction in women with
PCOS. The outcomes of interest include ovulation rates, pregnancy rates, and safety profiles,
which are crucial factors in guiding clinicians and patients towards informed treatment
decisions.

Furthermore, understanding the relative effectiveness and safety of these two

commonly used medications is essential for optimizing fertility interventions and improving
the overall reproductive health of women with PCOS.

Research Question:

Is there a significant difference in ovulation rates, occurrence of multiple pregnancies,

endometrial thickness, pregnancy rates, and side effects between clomiphene citrate and
letrozole for ovulation induction in women with PCOS?

7
 REVIEW OF LITERATURE

PCOS is one of the most common endocrinopathies in women of reproductive age,

affecting between 6.5 and 10 percent of women overall.20 In a meta-analysis of 55 population-
based studies from Europe, Australia, Asia, and the United States, the rates of hirsutism,
hyperandrogenemia, polycystic ovaries, and oligo-ovulation were 13, 11, 28, and 15 percent,
respectively.21 It is important to appreciate that PCOS is a syndrome, reflecting multiple
potential etiologies and variable clinical presentations. Its key features are oligo- or anovulation
and hyperandrogenism. Other features are polycystic ovaries on pelvic ultrasonography,
infertility due to oligo-ovulation, obesity, and insulin resistance.

The menstrual dysfunction in PCOS is characterized by oligo- or amenorrhea, caused

by infrequent or absent ovulation. The menstrual disturbances classically have a peripubertal
onset. Affected women may have a normal or slightly delayed menarche followed by irregular
cycles. Other women may apparently have regular cycles at first and subsequently develop
menstrual irregularity in association with weight gain. Although the mechanism is not fully
elucidated, many obese women with PCOS resume more regular menstrual cycles with even
modest weight loss.

The key ovarian findings in PCOS include multiple, small, preantral and antral follicles
in a peripheral location, with an increased volume of stroma. Histologically, there is a thickened
and sclerotic cortex of the ovary, giving the appearance of a smooth white capsule on gross
examination.22

The Rotterdam ultrasound criteria include the presence of 12 or more follicles in each
ovary measuring 2 to 9 mm in diameter and/or increased ovarian volume (>10 mL; calculated
using the formula 0.5 x length x width x thickness). Ovarian volume and follicle number
decrease with age in women with or without PCOS. Using the original ultrasound criteria in
combination with an ovarian volume greater than 10 mL (from revised criteria), nearly all
women with irregular menses and hyperandrogenism have polycystic ovaries on ultrasound.23

As a sole finding, sonographically detected polycystic ovaries are not sufficient to make
the diagnosis of PCOS, although they may represent a mild form of ovarian hyperandrogenism
and insulin resistance. This was illustrated in a study of 68 nonhirsute women with normal
menstrual cycles, 39 of whom had polycystic morphology on ultrasound.24 Serum total and free
testosterone and dehydroepiandrosterone sulfate (DHEAS) were higher in the early follicular
phase in women with polycystic morphology compared with those with normal ovarian

8
morphology. In addition, both fasting insulin and insulin resistance calculated from a
homeostasis model assessment of insulin resistance (HOMA-IR or HOMA model: fasting
glucose x fasting insulin) were higher in the women with polycystic morphology. In a follow-
up report from the same investigators, women with regular menstrual cycles and polycystic
ovaries on ultrasound were not at increased risk for subsequent development of PCOS.25

Women with PCOS have infrequent ovulation and, therefore, often take longer to
conceive. Many, if not most, women who have PCOS and oligo-ovulation and desire fertility
eventually undergo ovulation induction therapies. Women who have PCOS may have other
reasons for infertility as well since they have, in comparison with women with hypothalamic
amenorrhea, a reduced rate of conception relative to the rate of ovulation after therapy
with clomiphene citrate. Infertility was included in the original description of PCOS.26

Over the past 25 years, internationally accepted diagnostic criteria have been developed
for adults based on various combinations of otherwise unexplained hyperandrogenism,
anovulation, and a polycystic ovary, which are all encompassed by the Rotterdam consensus
criteria.

Sahu et al28 (2020) in a prospective randomized, parallel, comparative clinical trial of two
ovulation induction drugs letrozole 5 mg versus clomiphene citrate 100 mg as first-line
ovulation induction drug in infertile polycystic ovarian syndrome women reported that, In
letrozole group, the ovulation rate, mono-follicular development, mean endometrial thickness
and pregnancy rate was better in comparison to clomifene citrate group. Out of 50 patients in
letrozole group 38 patients ovulated accounting to 76%. Out of 50 patients in clomiphene group
26 patients ovulated accounting to 52%. 81.25% of the cases developed single follicle and
18.75% of the cases developed multiple follicles with letrozole. In clomiphene group, 32.65%
of the cases developed single follicle and 67.34% of the cases developed multiple follicles. The
mean endometrial thickness in letrozole group is 8.29 mm with a SD of 0.7836. In clomiphene
group the mean endometrial thickness is 7.18 mm with a SD of 0.7259. 24%of cases pregnancy
occurred in letrozole group and in clomiphene group 12% of cases pregnancy occurred.

Gupta et al29 (2020) studied the efficacy of letrozole versus clomiphene citrate (CC) for
ovulation induction in infertile women with PCOS among 92 women. The clinical profile of
patients belonging to both groups were comparable. The number of follicles ≥18mm on the day
of HCG was 1.11±0.43 for the letrozole group and 2.53±1.10 for the CC group (P<0.001).
Endometrial thickness on the day of HCG administration (mm) was higher in the letrozole

9
group than the CC group (P<0.001). Ovulation rate was higher in the letrozole group (P=0.047).
Urine pregnancy test (UPT) positive patients were 40.42% in the letrozole group and 20% in
the CC group (P=0.033). Clinical pregnancy rates were slightly higher in the letrozole group.
Higher twin pregnancy (P=0.025) and miscarriage rates were noted in the CC group (P=0.033).

Hegde et al30 (2020) aimed to compare the role of Clomiphene Citrate (CC) and Letrozole
in inducing ovulation in infertile patients with Polycystic Ovary Syndrome (PCOS).
Monofollicular development was statistically significantly greater in the Letrozole group (CC
61.9%, Letrozole 86.9%). There was also a statistically significant difference between the two
groups in endometrial thickness (CC 7.86±1.25mm, Letrozole 9.18±1.49mm). Similarly, the
ovulation rate was 84% in the CC group and 92% in the Letrozole group. The pregnancy rate
was 20% in the CC group and 36% in the Letrozole group.

Bansal et al31 (2021) compared the efficacy of letrozole and clomiphene citrate (CC) for
ovulation induction in infertile women with PCOS. It was observed in their study results that
Mean endometrial thicknesses were 9.86 ± 2.32 mm and 9.39 ± 2.06 mm with letrozole and
CC, respectively (P=0.751). Cumulative ovulation rates were 86.7% and 85.2% with letrozole
and CC, respectively (P=0.751). Pregnancy was achieved in 42.2% of women in the letrozole
group and 20.0% of women in the CC group (P=0.04). Monofollicular development was seen
in 68.4% of ovulatory cycles in the letrozole group compared with 44.8% in the CC group
(P=0.000). Mean time to achieve pregnancy was significantly shorter (log rank P=0.042) with
letrozole (9.65 weeks) than with CC (11.07 weeks).

Kabadi et al32 (2022) aimed to estimate effectiveness of clomiphene citrate versus

letrozole in ovulation induction. 60 women with infertility were randomised for treatment with
either letrozole or clomiphene citrate for ovulation induction. It was reported in their research
results that Ovulation rate was 80% with clomiphene citrate and 93.3% with letrozole. First
cycle conception rates with letrozole was higher (23.3%) compared to clomiphene citrate
(6.7%). Cumulative conception rate was 25% with clomiphene citrate and 32.1% with
letrozole. Pregnancy continuation and miscarriage rates were comparable in both groups.

Khatri et al33 (2023) evaluated fertility outcomes on ovulation induction with Clomiphene
Citrate versus Letrozole among anovulatory. A total of 106 patients were included in their
study, with 52 cases treated with Letrozole and 54 cases with Clomiphene. Most subjects in
either group had oligomenorrhea (57.4% & 61.4%) with regular cycles. Ovulation occurred in

10
27 (51.9%) subjects with Letrozole and 18 (33.3%) with Clomiphene. Successful pregnancy
outcomes were seen in 24 out of 52 (46.1%) with Letrozole and 16 out of 54 (29.6%) with
Clomiphene.

11
 AIM AND OBJECTIVES

Aim:

To compare the efficacy of clomiphene citrate and letrozole for ovulation induction in
women with polycystic ovarian syndrome (PCOS).

Objectives:

1 To assess and compare the ovulation rates achieved with clomiphene citrate and
letrozole in women diagnosed with PCOS.
2 To compare the endometrial thickness in response to clomiphene citrate and letrozole
during ovulation induction in PCOS patients.
3 To analyse the pregnancy rates, both clinical and ongoing, in women with PCOS treated
with clomiphene citrate and letrozole.
4 To assess the incidence and nature of side effects associated with clomiphene citrate
and letrozole in PCOS patients undergoing ovulation induction.

Null Hypothesis:

There is no significant difference in the overall effectiveness, safety, and reproductive

outcomes, including ovulation rates, occurrence of multiple pregnancies, endometrial
thickness, and side effects, between clomiphene citrate and letrozole for ovulation induction
in women diagnosed with PCOS.

12
 MATERIAL AND METHODS

Study setting:

The presents study will be undertaken in a tertiary care teaching hospital in Chandigarh,
North India. The hospital caters to population from Chandigarh and neighbouring districts of
Punjab and Haryana.

Study Population:

The study population will consist of women diagnosed with PCOS who are seeking
fertility treatment in the study hospital and meet the inclusion criteria.

Study design:

The study will be designed as a randomized controlled trial (RCT) by using computer
generated Randomization , where eligible participants will be assigned to either the clomiphene
citrate or letrozole intervention group to compare the efficacy and safety of the two drugs for
ovulation induction in women with PCOS.

Study sample:

64 patients satisfying eligibility criteria will comprise the study sample, who will be
randomised to either one of the study groups.

Sample Size estimation:

Considering the pregnancy rate for letrozole and clomiphene citrate from the study by
Jain et al,34 for an alpha error of 5%, and power of 80%, the minimum required sample size in
each group was calculated to be 32 per study group.

13
Where,

p1, p2 = proportion (incidence) of groups #1 and #2

Δ = |p2-p1| = absolute difference between two proportions
n1 = sample size for group #1
n2 = sample size for group #2
α = probability of type I error (0.05)
β = probability of type II error (0.2)
z = critical Z value for a given α or β
K = ratio of sample size for group #2 to group #1

Sampling technique:

All eligible to participants will be randomised one of the study groups using the
computer generated random numbers.

Study Period:

The present study will be undertaken during the period january 2024 to Mar 2025.

Inclusion Criteria:

 Women aged 18 to 35 years.

 Diagnosis of polycystic ovarian syndrome (PCOS) based on established clinical and/or

ultrasound criteria by Rotterdam criteria.

 Seeking fertility treatment due to anovulation associated with PCOS.

14
  Regular menstrual cycles (24-35 days) or oligomenorrhea.

 Body mass index (BMI) between 18.5 and 35 kg/m².

 Willingness to comply with the study protocol and provide informed consent.

Exclusion Criteria:

 Known hypersensitivity or contraindications to clomiphene citrate or letrozole.

 History of severe liver disease or abnormal liver function tests.
 Previous adverse reactions or poor response to clomiphene citrate or letrozole.
 Presence of other significant infertility factors unrelated to anovulation like uterine or
tubal factors.
 Use of ovulation-inducing agents within the past three months.
 Presence of ovarian cysts larger than 10 cm in diameter.
 Medical conditions contraindicating pregnancy.
 History of recurrent pregnancy loss.
 Significant male factor infertility.
 Current use of medications known to affect ovulation.

Pretreatment evaluation:

Before initiating therapy, the presence of ovulatory dysfunction must be established. The
menstrual history alone may be diagnostic (eg, one can be confident that ovulatory dysfunction
is present in women with amenorrhea or irregular menses [>45 day intermenstrual interval]).
It is possible that women with cycles in the 35- to 45-day range have intermittent ovulations.
We suggest that these women try to conceive on their own without therapy for several months.
If they are unsuccessful, they should be referred for ovulation induction. If the diagnosis of
ovulatory dysfunction is uncertain, additional testing should be performed. This can include
simple, non-invasive tests such as basal body temperature and/or urinary luteinizing hormone
(LH) monitoring, although a luteal phase serum progesterone level is more definitive.

Disorders of pituitary, adrenal, and thyroid origin that can cause anovulation should be
excluded prior to the initiation of therapy as targeted treatment of these endocrinopathies can
result in normal ovulation.

The pretreatment evaluation should include27:

15
 A complete history and physical examination,Laboratory testing: Human chorionic
gonadotropin (hCG), thyroid-stimulating hormone (TSH), and prolactin (PRL) to exclude
pregnancy, thyroid disease, and hyperprolactinemia as causes of the ovulatory dysfunction,
respectively, because these require different treatments. Serum follicle-stimulating hormone
(FSH) should also be measured as women diagnosed with primary ovarian insufficiency are
unlikely to respond to clomiphene.Women with PCOS and obesity should be screened for
diabetes and encouraged to lose weight before considering ovulation induction.Semen analysis
of the partner to identify seminal abnormalities that might contribute to the infertility.
Hysterosalpingogram if the clinical history suggests uterine or tubal pathology may also be
present and in women over 35 years of age to avoid ineffective treatment when fertility is in
decline. In women with no risk factors for tubal disease, the hysterosalpingogram can be
postponed but should be performed if women have not conceived after three ovulatory
cycles.An endometrial biopsy may be indicated to assess hyperplastic changes in women with
chronic anovulation. This is not routine, however. A pelvic examination or a pelvic ultrasound
to rule out ovarian cysts, especially in patients with known tendency to form functional
cysts.Some experts suggest an assessment of ovarian follicle pool in women over age 37 years.
A low serum anti-müllerian hormone (AMH) less than 1 ng/mL would identify a woman with
a diminished pool of oocytes who would likely be triaged to assisted reproductive interventions
(instead of clomiphene citrate).

Brief Procedure:

Patients will undergo clinical examination, including the measurement of height and
weight for calculating BMI (BMI = weight in kg/height in m^2). This reliable, inexpensive,
and easily performed indicator will be assessed for all participants. Clinical evidence of acne,
hirsutism, acanthosis nigricans, hyperthyroidism, and hypothyroidism will be examined.
Comprehensive blood tests, including complete blood count, random blood sugar, renal
function test, and liver function test, will be conducted for all enrolled patients.

Bilateral tubal patency will be assessed through hysterosalpingography (HSG), and

those with abnormal tubal patency will be excluded. Both groups will undergo transvaginal
ultrasonographic monitoring of the number of follicles and endometrial thickness from Day 9
onwards, by the same observer, and Human Chorionic Gonadotrophin will be administered at
a dose of 5,000 IU when at least 1 mature follicle (18-22mm) is detected. Timed intercourse
will be advised to the patients after 24-3 6hrs of hCG. If patients develop ovarian enlargement

16
or hyperstimulation, the treatment will be discontinued in both groups. The number of follicles,
ovulation rate, endometrial thickness, and pregnancy rate will be compared between the two
groups.

Operational definitions:

PCOS:

Rotterdam criteria will be used to make the diagnosis of PCOS.26

Two out of three of the following criteria are required to make the diagnosis.

● Oligo- and/or anovulation

● Clinical and/or biochemical signs of hyperandrogenism

● Polycystic appearing ovary (USG) Ovarian volume >10ml 3 and/or more

than 12 follicles between 2-9 mm in size in atleast 1 ovary.

Dosing: Before staring study CTRI(clinical Trials Registry-India) of Drugs

will be done .

(i) Letrozole will be administered at a starting dose of 2.5 mg/day on cycle days
3 to 7, following a spontaneous menses or progestin-induced bleed. In cases
where the cycle is ovulatory but pregnancy has not occurred, the same dose
will be used in the subsequent cycle. If ovulation does not occur, the dose
will be increased to 5 mg/day on cycle days 3 to 7, with a maximal dose of
7.5 mg/day. Sequential dose escalation of 2.5, 5, and 7.5 mg if ovulation
does not occur on lower doses, will be employed.Total 3 cycles will be
given.
(ii) Clomiphene citrate therapy for ovulation induction will be initiated on the
fifth day of a cycle, following either spontaneous or induced bleeding.
However, comparable results in terms of ovulatory rates, pregnancy, or
spontaneous miscarriage can be achieved when clomiphene is started on
cycle day 2, 3, 4, or 5.39,40 The initial dose will be 50 mg daily for five days.
If ovulation does not occur in the first cycle of treatment, the dose will be
increased to 100 mg. Subsequently, the dose will be increased by increments
of 50 mg to a maximum daily dose of 150 mg. Total 3 cycles will be given.

17
 STATISTICAL ANALYSIS

Means and proportions will be calculated for continuous and categorical variables
respectively. Difference in proportions will be tested for statistical significance using chi square
test. Difference in means will be tested using independent sample student t test. A p value <0.05
will be considered statistically significant. Data entry will be done using MS Excel 2016 and
data analysis will be carried out using IBM SPSS version 26.0

18
 ETHICAL JUSTIFICATION

A written and informed consent will be taken from all the women for participation in
the current study. The study will be adhere to the Central Ethics Council on Human Research’s
(CECHR) ethical standards for biomedical research involving human subjects as outlined in
the “Declaration of Helinski” and ICMR , New Delhi. The study project’s patient will be
willing volunteers. Each patient will get enough information about the study’s objectives,
procedures and expected outcomes, through participant information sheets. Every effort will
be made to protect the patient’s privacy and confidentiality of their information. The patient
will be given the right to opt out of the study at any time she wants without facing any
consequences. No extra costs will be charged to the patient. Institute ethical committee
clearance certificate will be sought and obtained before the study is begun. All the information
procured from the study will be kept confidential and used for academic purposes only.

19
 PATIENT INFORMATION SHEET

Patient Identification Number for this study:

Title of the Project: Comparison of clomiphene citrate & letrozole for
ovulation induction in polycystic ovarian syndrome

Name of the Researcher/Candidate: Dr khyati j parmar

Telephone No.: 9033671489
The contents of the information sheet dated:
You/ your patient is being invited to participate in the research study titled
“.Comparison of clomiphene citrate & letrozole for ovulation induction
in polycystic ovarian syndrome” being conducted at GMSH Sector 16, Chandigarh.
Procedure:
After complete clinical examination,laboratory tests,imaging tests patient with pcos will
be given clomiphene citrate or letrozole . from day 9 of cycle tvs will be done . if there will
be one mature follicle inj. HCG will be given,timed intercourse will be advised.
Benefits of participating in the study:
The study will be helpful in determining the most effective drug for ovulation induction in
infertility patient with pcos .
Risks: hot flushes, difficulty sleeping,tiredness,low mood, muscle weakness, OHSS,
frequent mouth ulcers,high temperature or chills.

Alternatives to participation:
You are free not to participate in the study or to opt out from the study at any time. Your
participation is voluntary and you are free to withdraw at any time, without giving any
reason, without your medical care and legal rights being affected in any way. You have the
right to refuse the individual procedures.
Confidentiality:
The information collected about you, from your participation in this research and sections
of any of your medical notes will be kept strictly confidential and used for scientific
purposes only. The information from this study, if published in scientific journals or
presented in any scientific meeting, will not reveal your identity.
For any further questions regarding the study, you can contact the investigator of the
study.
Dr khyati j parmar

20
परियोजना का शीर्षक: पॉलीसिस्टिक ओवेरियन सििंड्रोम में ओव्यूलेशन प्रेिण के सलए
क्लोमीफीन िाइट्र े ट् औि लेट्रोजोल की तुलना

शोधकताष/उम्मीदवाि का नाम: ड्ॉ ख्यासत जे पिमाि ट्े लीफोन निंबि: 9033671489

सदनािंसकत िूचना पत्र की िामग्री:

आपको/आपके मिीज को जीएमएिएच िेक्टि 16, चिंड्ीगढ़ में आयोसजत सकए जा िहे शोध
अध्ययन "पॉलीसिस्टिक ओवेरियन सििंड्रोम में इि अध्ययन के सलए िोगी पहचान ििंख्या:

ओव्यूलेशन इिं ड्क्शन के सलए क्लोमीफीन िाइट्र े ट् औि लेट्रोजोल की तुलना" में भाग लेने के
सलए आमिंसत्रत सकया जा िहा है ।

प्रसिया: पूणष नैदासनक पिीक्षण, प्रयोगशाला पिीक्षण, इमेसजिंग पिीक्षण के बाद पीिीओएि
वाले िोगी को क्लोमीफीन िाइट्र े ट् या लेट्रोजोल सदया जाएगा। िाइसकल के 9वें सदन िे ट्ीवी
सकया जाएगा। अगि वहााँ एक परिपक्व कूप इिं जे. होगा. एचिीजी सदया जाएगा, िमय पि
ििंभोग की िलाह दी जाएगी।

अध्ययन में भाग लेने के लाभ: यह अध्ययन पीिीओएि िे पीस़ित बािंझपन के िोसगयोिं में
ओव्यूलेशन प्रेिण के सलए िबिे प्रभावी दवा का सनधाषिण किने में िहायक होगा।

जोस्टिम: गमष चमक, िोने में कसिनाई, थकान, ििाब मूड्, मािंिपेसशयोिं में कमजोिी,
ओएचएिएि, बाि-बाि मुिंह में छाले, उच्च तापमान या ििं ड् लगना।

भागीदािी के सवकल्प: आप सकिी भी िमय अध्ययन में भाग न लेने या अध्ययन िे बाहि
सनकलने के सलए स्वतिंत्र हैं । आपकी भागीदािी स्वैस्टिक है औि आप सकिी भी िमय, सबना
कोई कािण बताए, अपनी सचसकत्सा दे िभाल औि कानूनी असधकािोिं को प्रभासवत सकए सबना
इिे वापि लेने के सलए स्वतिंत्र हैं। आपको व्यस्टिगत प्रसियाओिं िे इनकाि किने का असधकाि
है।

गोपनीयता : इि शोध में आपकी भागीदािी िे आपके बािे में एकत्र की गई जानकािी औि
आपके सकिी भी मेसड्कल नोट्् ि के अनुभागोिं को िख्ती िे गोपनीय ििा जाएगा औि केवल
वैज्ञासनक उद्दे श्ोिं के सलए उपयोग सकया जाएगा। इि अध्ययन की जानकािी, यसद वैज्ञासनक
पसत्रकाओिं में प्रकासशत की जाती है या सकिी वैज्ञासनक बैिक में प्रस्तुत की जाती है , तो इििे
आपकी पहचान उजागि नही िं होगी।

21
अध्ययन के ििंबिंध में सकिी भी अन्य प्रश्न के सलए, आप अध्ययन के अन्वेर्क िे ििंपकष कि
िकते हैं ।ड्ॉ ख्यासत जे पिमािਇਸ ਅਧਿਐਨ ਲਈ ਮਰੀਜ਼ ਪਛਾਣ ਨੰਬਰ:

ਪਰਜ
ੋ ੈਕਟ ਦਾ ਧਸਰਲੇ ਖ: ਪੋਲੀਧਸਸਧਟਕ ਅੰ ਡਕੋਸ਼ ਧਸੰ ਡਰੋਮ ਧ ਿੱ ਚ ਓ ਲ
ੂ ੇ ਸ਼ਨ ਇੰ ਡਕਸ਼ਨ ਲਈ ਕਲੋ ਮੀਫੇਨ ਧਸਟਰੇਟ ਅਤੇ
ਲੈ ਟਰੋਜ਼ਲ
ੋ ਦੀ ਤੁਲਨਾ

ਖੋਜਕਰਤਾ/ਉਮੀਦ ਾਰ ਦਾ ਨਾਮ: ਡਾ. ਧਖਆਤੀ ਜੇ ਪਰਮਾਰ ਟੈਲੀਫੋਨ ਨੰਬਰ: 9033671489

ਧਮਤੀ ਜਾਣਕਾਰੀ ਪਿੱ ਤਰ ਦੀ ਸਮਿੱ ਗਰੀ:

ਤੁਹਾਨੂੰ/ਤੁਹਾਡੇ ਮਰੀਜ਼ ਨੂੰ GMSH ਸੈਕਟਰ 16, ਚੰ ਡੀਗੜ੍ਹ ਧ ਖੇ ਕਰ ਾਏ ਜਾ ਰਹੇ ਖੋਜ ਅਧਿਐਨ “ਕਲੋ ਮੀਫੇਨ
ਧਸਟਰੇਟ ਅਤੇ ਲੈ ਟਰੋਜ਼ਲ
ੋ ਫਾਰ ਓ ਲ
ੂ ੇ ਸ਼ਨ ਇੰ ਡਕਸ਼ਨ ਇਨ ਪੋਲੀਧਸਸਧਟਕ ਓ ਰ
ੇ ੀਅਨ ਧਸੰ ਡਰੋਮ” ਧ ਿੱ ਚ ਭਾਗ ਲੈ ਣ
ਲਈ ਸਿੱ ਦਾ ਧਦਿੱ ਤਾ ਜਾ ਧਰਹਾ ਹੈ।

ਪਰਧਕਧਰਆ: ਪੂਰੀ ਕਲੀਧਨਕਲ ਜਾਂਚ, ਪਰਯਗ

ੋ ਸ਼ਾਲਾ ਦੇ ਟੈਸਟ, ਇਮੇਧਜੰ ਗ ਟੈਸਟਾਂ ਤੋਂ ਬਾਅਦ ਪੀਸੀਓਐਸ ਾਲੇ ਮਰੀਜ਼
ਨੂੰ ਕਲੋ ਮੀਫੇਨ ਧਸਟਰੇਟ ਜਾਂ ਲੈ ਟਰੋਜ਼ਲ
ੋ ਧਦਿੱ ਤਾ ਜਾ ਗ
ੇ ਾ। ਚਿੱ ਕਰ ਦੇ 9 ੇਂ ਧਦਨ ਤੋਂ ਟੀ. ੀ. ਜੇਕਰ ਕੋਈ ਪਧਰਪਿੱ ਕ
ਫੋਲੀਕਲ ਇੰ ਜ. ਹੋ ਜਾ ਗ
ੇ ਾ. HCG ਧਦਿੱ ਤਾ ਜਾ ਗ
ੇ ਾ, ਸਮੇਂ ਧਸਰ ਸੰ ਭੋਗ ਦੀ ਸਲਾਹ ਧਦਿੱ ਤੀ ਜਾ ਗ
ੇ ੀ।

ਅਧਿਐਨ ਧ ਚ ਧਹਿੱ ਸਾ ਲੈ ਣ ਦੇ ਲਾਭ: ਇਹ ਅਧਿਐਨ PCOS ਤੋਂ ਪੀੜ੍ਤ ਬਾਂਝਪਨ ਾਲੇ ਮਰੀਜ਼ਾਂ ਧ ਿੱ ਚ ਓ ਲ
ੂ ੇ ਸ਼ਨ
ਇੰ ਡਕਸ਼ਨ ਲਈ ਸਭ ਤੋਂ ਪਰਭਾ ਸ਼ਾਲੀ ਦ ਾਈ ਦਾ ਪਤਾ ਲਗਾਉਣ ਧ ਿੱ ਚ ਮਦਦਗਾਰ ਹੋ ਗ
ੇ ਾ।

ਜੋਖਮ: ਗਰਮ ਚਮਕ, ਸੌਣ ਧ ਿੱ ਚ ਮੁਸ਼ਕਲ, ਥਕਾ ਟ, ਖਰਾਬ ਮੂਡ, ਮਾਸਪੇਸ਼ੀਆਂ ਦੀ ਕਮਜ਼ੋਰੀ, OHSS, ਾਰ- ਾਰ ਮੂੰ ਹ
ਦੇ ਫੋੜ੍,ੇ ਉੱਚ ਤਾਪਮਾਨ ਜਾਂ ਠੰਢ ਲਿੱਗਣਾ।

ਭਾਗੀਦਾਰੀ ਦੇ ਧ ਕਲਪ:

ਤੁਸੀਂ ਧਕਸੇ ੀ ਸਮੇਂ ਅਧਿਐਨ ਧ ਿੱ ਚ ਧਹਿੱ ਸਾ ਲੈ ਣ ਜਾਂ ਾਪਸ ਨਾ ਲੈ ਣ ਲਈ ਸੁਤੰਤਰ ਹੋ। ਤੁਹਾਡੀ ਭਾਗੀਦਾਰੀ ਸ ਇ
ੈ ਿੱ ਛਤ
ਹੈ ਅਤੇ ਤੁਸੀਂ ਧਕਸੇ ੀ ਸਮੇਂ, ਧਬਨਾਂ ਕੋਈ ਕਾਰਨ ਦਿੱ ਸੇ, ਤੁਹਾਡੀ ਡਾਕਟਰੀ ਦੇਖਭਾਲ ਅਤੇ ਕਾਨੂੰਨੀ ਅਧਿਕਾਰਾਂ ਨੂੰ
ਪਰਭਾਧ ਤ ਕੀਤੇ ਧਬਨਾਂ ਾਪਸ ਲੈ ਣ ਲਈ ਸੁਤੰਤਰ ਹੋ। ਤੁਹਾਨੂੰ ਧ ਅਕਤੀਗਤ ਪਰਧਕਧਰਆ ਾਂ ਤੋਂ ਇਨਕਾਰ ਕਰਨ ਦਾ
ਅਧਿਕਾਰ ਹੈ।

ਗੋਪਨੀਯਤਾ: ਇਸ ਖੋਜ ਧ ਿੱ ਚ ਤੁਹਾਡੀ ਭਾਗੀਦਾਰੀ ਤੋਂ ਤੁਹਾਡੇ ਬਾਰੇ ਇਕਿੱ ਠੀ ਕੀਤੀ ਗਈ ਜਾਣਕਾਰੀ ਅਤੇ ਤੁਹਾਡੇ ਧਕਸੇ
ੀ ਮੈਡੀਕਲ ਨੋਟਸ ਦੇ ਭਾਗਾਂ ਨੂੰ ਸਖਤੀ ਨਾਲ ਗੁਪਤ ਰਿੱ ਧਖਆ ਜਾ ਗ
ੇ ਾ ਅਤੇ ਧਸਰਫ ਧ ਧਗਆਨਕ ਉਦੇਸ਼ਾਂ ਲਈ
ਰਧਤਆ ਜਾ ਗ
ੇ ਾ। ਇਸ ਅਧਿਐਨ ਤੋਂ ਜਾਣਕਾਰੀ, ਜੇਕਰ ਧ ਧਗਆਨਕ ਰਸਾਧਲਆਂ ਧ ਿੱ ਚ ਪਰਕਾਧਸ਼ਤ ਕੀਤੀ ਜਾਂਦੀ ਹੈ
ਜਾਂ ਧਕਸੇ ਧ ਧਗਆਨਕ ਮੀਧਟੰ ਗ ਧ ਿੱ ਚ ਪੇਸ਼ ਕੀਤੀ ਜਾਂਦੀ ਹੈ, ਤਾਂ ਤੁਹਾਡੀ ਪਛਾਣ ਪਰਗਟ ਨਹੀਂ ਹੋ ਗ
ੇ ੀ। ਅਧਿਐਨ
ਸੰ ਬੰ ਿੀ ਧਕਸੇ ੀ ਹੋਰ ਸ ਾਲਾਂ ਲਈ, ਤੁਸੀਂ ਅਧਿਐਨ ਜਾਂਚਕਰਤਾ ਨਾਲ ਸੰ ਪਰਕ ਕਰ ਸਕਦੇ ਹੋ।

22
ਧਖਆਤੀ ਜੇ ਪਰਮਾਰ ਨੇ ਡਾ

PATIENT INFORMED CONSENT FORM

Patient identification number for this trial:

Title of the project: “.Comparison of clomiphene citrate & letrozole for ovulation
induction in polycystic ovarian syndrome

Name of Principal Investigator:

The contents of the information sheet dated …………………………………..that was provided have
been read carefully by me / explained in detail to me, in a language that I comprehend, and
I have fully understood the contents. I confirm that I have the opportunity to ask questions.
The nature and purpose of the study and its potential risks/ benefits and expected duration
of the study, and the other relevant details of the study have been explained to me in detail.
I understand that my participation is voluntary and that I am free to withdraw at any time,
without giving any reason, without my medical care being affected.
I understand that the information collected about me from my participation in this research
and sections of any of my medical notes may be looked at by law. I give permission for these
individuals to have access to my records.
I agree to take part in the above study.

………………………………………………………….. Date:
(Signature/Left Thumb Impression) Place:
CHANDIGARH
Name of the Participant:
Daughter/ Spouse of:
Complete postal address:

This is to certify that the above consent has been obtained in my presence.
Signature of Dr khyati Place:
1) Witness -1 2) Witness-2
Signature Signature
Name: Name:

23
िोगी िूसचत िहमसत प्रपत्र

इि पिीक्षण के सलए िोगी पहचान ििंख्या:

परियोजना का शीर्षक: "पॉलीसिस्टिक ओवेरियन सििंड्रोम में ओव्यूलेशन प्रेिण के सलए

क्लोमीफीन िाइट्र े ट् औि लेट्रोजोल की तुलना

प्रधान अन्वेर्क का नाम:

सदनािंक ……………………………….. प्रदान की गई िूचना शीट् की िामग्री को मेिे द्वािा ध्यान

िे पढ़ा गया है / मुझे मेिी िमझ में आने वाली भार्ा में सवस्ताि िे िमझाया गया है , औि मैं
पूिी तिह िे िमझ गया हिं िामसग्रयािं। मैं पुसि किता हिं सक मुझे प्रश्न पूछने का अविि समला है।

अध्ययन की प्रकृसत औि उद्दे श् औि इिके ििंभासवत जोस्टिम/लाभ औि अध्ययन की

अपेसक्षत अवसध, औि अध्ययन के अन्य प्राििंसगक सवविण मुझे सवस्ताि िे बताए गए हैं। मैं
िमझता हिं सक मेिी भागीदािी स्वैस्टिक है औि मैं सकिी भी िमय, सबना कोई कािण बताए,
अपनी सचसकत्सा दे िभाल को प्रभासवत सकए सबना वापि लेने के सलए स्वतिंत्र हिं ।

मैं िमझता हिं सक इि शोध में मेिी भागीदािी िे मेिे बािे में एकत्र की गई जानकािी औि मेिे
सकिी भी मेसड्कल नोट् के अनुभागोिं को कानून द्वािा दे िा जा िकता है । मैं इन व्यस्टियोिं को
मेिे रिकॉड्ष तक पहिंच की अनुमसत दे ता हिं ।

मैं उपिोि अध्ययन में भाग लेने के सलए िहमत हिं।

………………………………………………………….. तािीि:

(हस्ताक्षि/बाएिं अिंगूिे का सनशान) स्थान:

चिंड्ीगढ़

प्रसतभागी का नाम:

की बेट्ी/पसत/पत्नी:

पूिा ड्ाक पता:

प्रमासणत सकया जाता है सक उपिोि िहमसत मेिी उपस्टस्थसत में प्राप्त की गई है ।

ड्ॉ. ख्यासत के हस्ताक्षि स्थान:

24
 1) गवाह-1 2) गवाह-2

ਮਰੀਜ਼ ਨੂੰ ਸੂਧਚਤ ਸਧਹਮਤੀ ਫਾਰਮ ਇਸ ਅਜ਼ਮਾਇਸ਼ ਲਈ ਮਰੀਜ਼ ਪਛਾਣ ਨੰਬਰ:

ਪਰਜ
ੋ ਕ
ੈ ਟ ਦਾ ਧਸਰਲੇ ਖ: “. ਪੌਲੀਧਸਸਧਟਕ ਅੰ ਡਕੋਸ਼ ਧਸੰ ਡਰੋਮ ਧ ਿੱ ਚ ਓ ਲ
ੂ ੇ ਸ਼ਨ ਇੰ ਡਕਸ਼ਨ ਲਈ ਕਲੋ ਮੀਫੇਨ ਧਸਟਰੇਟ
ਅਤੇ ਲੈ ਟਰੋਜ਼ਲ
ੋ ਦੀ ਤੁਲਨਾ

ਪਰਮਖ ੁਿੱ ਜਾਂਚਕਰਤਾ ਦਾ ਨਾਮ:

ਧਮਤੀ ………………………………….. ਪਰਦਾਨ ਕੀਤੀ ਗਈ ਜਾਣਕਾਰੀ ਸ਼ੀਟ ਦੀਆਂ ਸਮਿੱ ਗਰੀਆਂ ਨੂੰ ਮੇਰੇ ਦੁਆਰਾ ਧਿਆਨ
ਨਾਲ ਪਧੜ੍ਹਆ ਧਗਆ/ਧ ਸਥਾਰ ਨਾਲ ਸਮਝਾਇਆ ਧਗਆ, ਅਧਜਹੀ ਭਾਸ਼ਾ ਧ ਿੱ ਚ ਜੋ ਮੈਂ ਸਮਝਦਾ ਹਾਂ, ਅਤੇ ਮੈਂ ਪੂਰੀ ਤਰਹਾਂ
ਸਮਧਝਆ ਹਾਂ। ਸਮਿੱ ਗਰੀ. ਮੈਂ ਪੁਸ਼ਟੀ ਕਰਦਾ/ਕਰਦੀ ਹਾਂ ਧਕ ਮੇਰੇ ਕੋਲ ਸ ਾਲ ਪੁਿੱ ਛਣ ਦਾ ਮੌਕਾ ਹੈ।

ਅਧਿਐਨ ਦੀ ਪਰਧਕਰਤੀ ਅਤੇ ਉਦੇਸ਼ ਅਤੇ ਇਸਦੇ ਸੰ ਭਾ ੀ ਖਤਰੇ/ਲਾਭ ਅਤੇ ਅਧਿਐਨ ਦੀ ਸੰ ਭਾਧ ਤ ਧਮਆਦ, ਅਤੇ
ਅਧਿਐਨ ਦੇ ਹੋਰ ਸੰ ਬੰ ਧਿਤ ਰ
ੇ ਧ ਆਂ ਬਾਰੇ ਮੈਨੰ ੂ ਧ ਸਥਾਰ ਨਾਲ ਸਮਝਾਇਆ ਧਗਆ ਹੈ। ਮੈਂ ਸਮਝਦਾ/ਸਮਝਦੀ ਹਾਂ
ਧਕ ਮੇਰੀ ਭਾਗੀਦਾਰੀ ਸ ਇ
ੈ ਿੱ ਛਤ ਹੈ ਅਤੇ ਇਹ ਧਕ ਮੈਂ ਧਕਸੇ ੀ ਸਮੇਂ, ਧਬਨਾਂ ਕੋਈ ਕਾਰਨ ਦਿੱ ਸੇ, ਮੇਰੀ ਡਾਕਟਰੀ ਦੇਖਭਾਲ
ਨੂੰ ਪਰਭਾਧ ਤ ਕੀਤੇ ਧਬਨਾਂ ਾਪਸ ਲੈ ਣ ਲਈ ਸੁਤੰਤਰ ਹਾਂ।

ਮੈਂ ਸਮਝਦਾ/ਸਮਝਦੀ ਹਾਂ ਧਕ ਇਸ ਖੋਜ ਧ ਿੱ ਚ ਮੇਰੀ ਭਾਗੀਦਾਰੀ ਤੋਂ ਮੇਰੇ ਬਾਰੇ ਇਕਿੱ ਤਰ ਕੀਤੀ ਗਈ ਜਾਣਕਾਰੀ ਅਤੇ
ਮੇਰੇ ਧਕਸੇ ੀ ਮੈਡੀਕਲ ਨੋਟਸ ਦੇ ਭਾਗਾਂ ਨੂੰ ਕਾਨੂੰਨ ਦੁਆਰਾ ਦੇਧਖਆ ਜਾ ਸਕਦਾ ਹੈ। ਮੈਂ ਇਹਨਾਂ ਧ ਅਕਤੀਆਂ ਨੂੰ ਮੇਰੇ
ਧਰਕਾਰਡਾਂ ਤਿੱ ਕ ਪਹੁੰ ਚ ਕਰਨ ਦੀ ਇਜਾਜ਼ਤ ਧਦੰ ਦਾ ਹਾਂ।

ਮੈਂ ਉਪਰੋਕਤ ਅਧਿਐਨ ਧ ਿੱ ਚ ਧਹਿੱ ਸਾ ਲੈ ਣ ਲਈ ਸਧਹਮਤ ਹਾਂ।

………………………………………………………….. ਤਾਰੀਖ਼:

(ਦਸਤਖਤ/ਖਿੱ ਬੇ ਅੰ ਗੂਠੇ ਦਾ ਧਨਸ਼ਾਨ) ਸਥਾਨ:

ਚੰ ਡੀਗੜ੍ਹ

ਭਾਗੀਦਾਰ ਦਾ ਨਾਮ:

ਦੀ ਿੀ/ ਜੀ ਨ ਸਾਥੀ:

ਪੂਰਾ ਡਾਕ ਪਤਾ:

ਇਹ ਤਸਦੀਕ ਕਰਨ ਲਈ ਹੈ ਧਕ ਉਪਰੋਕਤ ਸਧਹਮਤੀ ਮੇਰੀ ਮੌਜਦ

ੂ ਗੀ ਧ ਿੱ ਚ ਪਰਾਪਤ ਕੀਤੀ ਗਈ ਹੈ।

ਧਖਆਤੀ ਸਥਾਨ ਦੇ ਦਸਤਖਤ: ਡਾ. 1) ਗ ਾਹ -1 2) ਗ ਾਹ -2

25
 PROFORMA
Name: Age: Occupation:
Address: IP/OP no: Date:
Phone no: Case no:
Clinical Details
History of
• Primary /secondary infertility since
• Oligomenorrhea/irregular periods
• Hirsutism

Obstetric history

1) Married since : 2) No. of children: 3) Parity

4) gestational age
5) LMP :
6) EDD:

4) Menstrual history
1) Age of menarche:

2) Menstrual cycle: Regular Irregular

Past history :H/O TB , DM, Hypertension , any previous surgeries: YES NO

General Physical Examination

Temprature:
Pulse: BP:

Pallor: YES NO
Icterus: YES NO

Lymphadenopathy : YES NO
Oedema : YES NO

26
 Weight: Height: BMI:
Systemic Examination :
CVS:
RS:
CNS:
Local Examination :
Per abdomen Examination:
Per speculum Examination:
Per vaginal Examination :
Provisional Clinical Diagnosis:
Investigations:
Hb%: TLC:
DLC: Platelet
count:
Blood Picture
BT/CT:
LFT:
RFT:
Coagulation Profile:
Urine- Albumin: Sugar:
Microscopy:
Thyroid Function Tests:
OGTT:
Viral markers:

USG Pelvis done: YES NO

Findings:
HSG FINDINGDS -

27
 Folliculometry chart
First cycle:
Dose used :
DATE DAY OF RIGHT LEFT ET FREE REMARKS
CYCLE OVARY OVARY FLUID IN /follow up
POD

Second cycle:
Dose used:
DATE DAY OF RIGHT LEFT ET FREE REMARKS
CYCLE OVARY OVARY FLUID IN /follow up
POD

Third cycle:
Dose used :

DATE DAY OF RIGHT LEFT ET FREE REMARKS

CYCLE OVARY OVARY FLUID IN /follow up
POD

28
 REFERENCES

1. Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P, et al.
Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J
Med 2014;371(2):119-29.
2. Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole)
for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev
2018;5(5):Cd010287.
3. Badawy A, Abdel Aal I, Abulatta M. RETRACTED: Clomiphene citrate or letrozole
for ovulation induction in women with polycystic ovarian syndrome: a prospective
randomized trial. Fertil Steril 2009;92(3):849-52.
4. He D, Jiang F. Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary
syndrome. Reprod Biomed Online 2011;23(1):91-6.
5. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352(12):1223-36.
6. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and
phenotypic features of polycystic ovary syndrome: a systematic review and meta-
analysis. Human reproduction (Oxford, England) 2016;31(12):2841-55.
7. Poruondo JA, Tejada RF, Benito JA, Bilbao FJ. Laparoscopy, ovarian and endometrial
biopsies in secondary amenorrhea. Endoscopy 1982;14(6):209-11.
8. Welt CK, Arason G, Gudmundsson JA, Adams J, Palsdóttir H, Gudlaugsdóttir G, et al.
Defining constant versus variable phenotypic features of women with polycystic ovary
syndrome using different ethnic groups and populations. The Journal of clinical
endocrinology and metabolism 2006;91(11):4361-8.
9. Adams JM, Taylor AE, Crowley WF, Jr., Hall JE. Polycystic ovarian morphology with
regular ovulatory cycles: insights into the pathophysiology of polycystic ovarian
syndrome. The Journal of clinical endocrinology and metabolism 2004;89(9):4343-50.
10. Murphy MK, Hall JE, Adams JM, Lee H, Welt CK. Polycystic ovarian morphology in
normal women does not predict the development of polycystic ovary syndrome. The
Journal of clinical endocrinology and metabolism 2006;91(10):3878-84.
11. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries.
American journal of obstetrics and gynecology 1935;29(2):181-91.

29
12. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril
2013;100(2):341-8.
13. Sahu M, Rout NR. Comparative study of clomiphene citrate versus letrozole as first-
line ovulation induction drug in infertile polycystic ovary syndrome women.
International Journal of Reproduction, Contraception, Obstetrics and Gynecology
2020;9(7):2948-53.
14. Gupta E, Nayar K, Singh M, Gupta S, Bhattacharya R. To study the comparison of
efficacy of letrozole versus clomiphene citrate for ovulation induction in infertile
women with PCOS in Indian population. Fertility Science and Research 2020;7(2):162-
8.
15. Hegde R, Maitra C. Comparison of the role of letrozole & clomiphene citrate as a first
line ovulation induction drug in infertile women with polycystic ovary syndrome.
Indian J Obstet Gynecol Res 2020;7(1):12-5.
16. Bansal S, Goyal M, Sharma C, Shekhar S. Letrozole versus clomiphene citrate for
ovulation induction in anovulatory women with polycystic ovarian syndrome: A
randomized controlled trial. International Journal of Gynecology & Obstetrics
2021;152(3):345-50.
17. Kabadi YKM, Madinoor PS. Randomized interventional clinical trial to estimate the
efficacy of clomiphene citrate versus letrozole in induction of ovulation in infertility.
The New Indian Journal of OBGYN 2022;9(1):94-8.
18. Khatri J, Ranjan K, Siddique S, Najam R. Comparative study of fertility outcomes on
ovulation induction with clomiphene citrate versus letrozole among anovulatory
polycystic ovarian syndrome women. Trends Clin Med Sci 2023SI:Indian Medical
Research Views & Findings on Last 5 years):348-54.
19. Jain S, Dahiya P, Yadav J, Jain N. A comparative study of efficacy of letrozole and
clomiphene citrate for ovulation induction. International Journal of Reproduction,
Contraception, Obstetrics and Gynecology 2018;7(10):4133-9.
20. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al.
Recommendations from the international evidence-based guideline for the assessment
and management of polycystic ovary syndrome. Fertil Steril 2018;110(3):364-79.
21. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al.
Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical
practice guideline. The Journal of clinical endocrinology and metabolism
2013;98(12):4565-92.
30
22. Revised 2003 consensus on diagnostic criteria and long-term health risks related to
polycystic ovary syndrome (PCOS). Human reproduction (Oxford, England)
2004;19(1):41-7.
23. Al-Fadhli R, Sylvestre C, Buckett W, Tan SL, Tulandi T. A randomized trial of
superovulation with two different doses of letrozole. Fertil Steril 2006;85(1):161-4.
39.Wu CH, Winkel CA. The effect of therapy initiation day on clomiphene citrate
therapy. Fertil Steril 1989;52(4):564-8.
24. Dehbashi S, Vafaei H, Parsanezhad MD, Alborzi S. Time of initiation of clomiphene
citrate and pregnancy rate in polycystic ovarian syndrome. International journal of
gynaecology and obstetrics: the official organ of the International Federation of
Gynaecology and Obstetrics 2006;93(1):44-8.

25. Ai-Min Yang,Na Cui,Yi-Fei Sun , Letrozole for Female infertility . Department for
Reproductive medicine , Shijiahuang , China .

26. Jacob P.Christ and Marcelle I. Cedars ,CURRENT Guidelines for Diagnosis of PCOS.
Department of Obstetrics , Gynecology , University of callifirnia ,USA

31
 ANNEXURES

Rotterdam criteria 26

Two out of three of the following criteria are required to make the diagnosis.

● Oligo- and/or anovulation

● Clinical and/or biochemical signs of hyperandrogenism

● Polycystic appearing ovary (USG) Ovarian volume >10ml 3 and/or more

than 12 follicles between 2-9 mm in size in atleast 1 ovary.