PCONCT04887402
Parameters Declaring PCO Infertile Patients Either Sensitive or Resistant to Different Doses of Clomiphene Citrate.
An observational study of PCO and Induction of Ovulation, run by Ain Shams Maternity Hospital at 1 site in Egypt.
Trial summary
Polycystic ovary syndrome (PCOS) is a common endocrinological disorder seen in 6%-10% of women (Human Reproduction, 2004). It is characterized by polycystic ovaries, anovulatory cycles, and hyperandrogenism. In nearly 20% of infertile women, PCOS is said to be the key reason behind infertility (Norman et al., 2007). Read more about this study
- Who is it for?
- Ages Up to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- PCO, Induction of Ovulation, Clomiphene Citrate
- What is being tested?
- Clomiphene Citrate
- Type of treatment
- Pill or oral medicine
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2021to Mar 2022
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 40 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Study population: The study will include 100 women with PCO Using PASS 11 program for sample size calculation and according to (sachdeva etal,2019), the expected frequency of PCOs patients with CC resistance = 54%, assuming that frequency in study population =54%+\- 10% and at 95% confidence level, sample size of 100 patients will be enough to detect this frequency.
Who may be able to join
- PCOS (based on Rotterdam's criteria: oligo/anovulation, hyperandrogenism clinical (hirsutism or less commonly male pattern alopecia) /biochemical (raised FAI or free testosterone) or polycystic ovaries on ultrasound(presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter, and/or increased ovarian volume (>10 ml)"1 . Unilaterality does not affect diagnosis; neither does the location of the cysts in the ovary.)
- Age <40 years.
- Semen analysis within normal according to WHO 2010.
Who cannot join
- Women on any insulin-sensitizing agent.
- Women on lipid-lowering agent.
- Women with endocrinal disorder (such as thyroid dysfunction, insulin resistance(DM), and adrenal disorders).
- Women diagnosed with anorexia nervosa/bulimia nervosa.
- Women with hypothalamic or pituitary dysfunction.
- Age >40
- AMH level that does not reflect the phenotype of PCO
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Ain Shams University
Cairo
Alaa Sherif Elsewafy, Master, 01114860044 ext. 002, dr_2laa_sherif@hotmail.com
Ahmed Rateb, professor, 01123600576 ext. 002, rateba@hotmail.com
About this study
Official title: Different Variables Predicting Ovulatory Response Among Clomiphene Citrate Resistance and Clomiphene Citrate Sensitive Patients With Polycystic Ovarian Syndrome.
Polycystic ovary syndrome (PCOS) is a common endocrinological disorder seen in 6%-10% of women (Human Reproduction, 2004). It is characterized by polycystic ovaries, anovulatory cycles, and hyperandrogenism.
In nearly 20% of infertile women, PCOS is said to be the key reason behind infertility (Norman et al., 2007).
Read more
PCOS is a syndrome that manifests variably from adolescence as oligomenorrhea or hirsutism or obesity and goes on to affect the reproductive performance of the female by causing anovulation. Some may even be severely affected by metabolic syndrome, diabetes mellitus, or endometrial carcinoma. It also increases the risk of ovarian and breast carcinoma (Atiomo et al., 2003).
PCOS falls in WHO type II anovulation (norm-gonadotropic norm-estrogenic anovulation) and is seen in 85% of anovulatory females. Although lifestyle modification is known to improve reproductive outcomes in females with PCOS, the gold standard treatment for norm-gonadotropic oligo/amenorrheic infertility (WHO Group II) was clomiphene citrate (CC) (Radosh L., 2009) until 2018, when ESHRE and ASRM have declared letrozole as the first-line treatment for ovulation induction (OI)( ESHRE 2018 guidelines).
To conclude, available data shows that letrozole is at least as effective as CC for ovulation and has comparable live birth rates. Importantly, it has definite advantages over CC. Many studies have shown letrozole to be as effective as gonadotropins, with added advantage of low cost and lower multiple pregnancy rates. However, the quality of medical evidence supporting aromatase inhibitors for OI, are inadequate, small in sample size, and inappropriate design. Moreover, there is very limited data on potential teratogenic effects, oocyte, embryo quality, and any effect on implantation. ( Misso et al., 2012) Those who fail to respond to CC are labeled as clomiphene resistant. It is common in approximately 15%-40% of women with PCOS (NICE, 2014). Major factors postulated for CC resistance include obesity, insulin resistance, (seen in nearly 50%-70% of females with PCOS) and hyperandrogenemia (Parsanezhad et al., 2001).Moreover, genetic predisposition is suggested to play a role in CC resistance (Overbeek et al., 2009).However, still, the current data available on the causes of CC resistance are not sufficient enough to direct our treatment.
It is seen in various studies (Sohrevardi et al.,2016) that the females who initially failed to respond to CC develop better ovulation and pregnancy outcomes on treatment with insulin-sensitizing agents. This indicates that insulin resistance may be a cause of CC resistance in females with PCOS. In fact, insulin-sensitizing agents (Azziz et al., 2009) decrease the dose of ovulation-inducing agent and time for follicular maturation in females with PCOS.
As of now, there have been no concrete studies to compare the metabolic profile of females who respond to CC and those who do not. It is still an enigma as to why some women respond to clomiphene, while others do not. By identifying the various factors which affect the response of CC in patients with infertility, a lot of time can be saved by giving alternate options of treatment to these patients. This study was done with the aim to analyze various clinical, metabolic, hormonal, and ultrasound parameters that might affect the response to clomiphene.
Read the detailed description
All PCO patients under the age of 40 who are subfertile with no identified cause but PCO will undergo the following;
- Detailed history taking including age, parity, medical, surgical history, previous trials of induction of ovulation.
- Physical examination:
- Vital data: blood pressure
- General examination: including weight in kilograms, and height in an upright posture without shoes using to the nearest 0.5 cm will be recorded. Body mass index (BMI) will be recorded from the above measurements. Waist circumference (WC) will be measured midway between the lower rib margin and the iliac crest in the mid-axillary line at the end of normal expiration. Hip circumference will be measured with the measuring tape at the highest prominence of the buttocks and parallel to the floor (Nishida et al., 2010). WC and hip circumference will be recorded after removing clothing from the area over the waist and hip.
The thyroid will be examined for any enlargement, nodules, or tenderness. The breast will be examined for any enlargement or galactorrhea. Signs of androgen excess will be looked for such as; excessive hair growth, acne, or alopecia. Excessive hair growth will be evaluated by modified Ferriman and Gallwey (Wild et al., 2004) (FG) score(<8 normal,8-15mild hirsutism,>15 moderate/severe hirsutism).
- Abdominal examination: including the presence of previous scars, uterine size, any tenderness, and presence of palpable masses, score on Ferriman Gallway scoring system.
- Pelvic examination: including uterine size, any adnexal mass, and tenderness, score on Ferriman Gallway scoring system.
- Investigation:
- Laboratory (on the 2nd day of cycle):
- Serum testosterone
- Androstenedione
- AMH
- LH
- FSH
- Fasting and 2hrs postprandial b) Imaging -Transvaginal ultrasound(on the 2nd day of cycle):
- Antral follicular count (AFC)
- Ovarian volume
- Endometrial thickness Will be done by the same observer using a Samsung ultrasound machine, HS40 (TVS probe frequency range 5-7 MHZ). The ovarian volume of each ovary will be assessed by ellipsoid formula, i.e., 0.52 × D1 (longitudinal) × D2 (oblique) × D3 (transverse) diameters. Mean ovarian volume will be calculated by adding the volume of both ovaries and then dividing it by 2. A note of ovarian follicles in each ovary will be also made and a total number of the follicles will be counted by scanning each ovary from the inner to the outer margin in longitudinal cross-section. Mean follicle number will be calculated by adding the follicles of both ovaries and then dividing it by 2.
- Method (stair step protocol):
All patients will be treated with CC starting with 50 mg/day on day 2 of their cycle for 5 days, a transvaginal ultrasound will be done 1 week after the last pill, if all follicles are below 10 mm the dose will subsequently be increased to 100mg/day for 5 days then 150mg/day for 5 days if a transvaginal is done a week from the last pill and showed no response (all follicles being below 10 mm ). The maximum cc dose will be 150 mg (ASRM, 2013). Medroxyprogesterone (10 mg/d Provera for 10 days)will be given to induce withdrawal bleeding to start these steps again in a new cycle. These steps will be repeated for 3cycles before declaring the patient CC resistant.
- Response: Response to CC will be assessed by ovulation. TVS will be done by the same observer using a Samsung ultrasound machine, HS40.
A scan will be done 1 week after the last pill of each dose. No response: if all follicles are below 10 mm (ASRM, 2013), follicles >10mm, follow up till ovulation Based on the ovulation pattern, these patients will be divided into two groups, one who ovulated with CC maximum 150 mg and others who did not ovulate considered as CC resistant. The patients who ovulated will be further classified into three subgroups based on whether they ovulated with 50 mg or 100 mg or 150 mg of CC.
The various parameters will be compared between the CC-resistant and CC-sensitive groups.
- Conditions
- PCO, Induction of Ovulation, Clomiphene Citrate
- Being tested
- Clomiphene Citrate
- Keywords
- induction of ovulation by clomiphene citrate in PCO
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomiphene CitrateDrug
All patients will be treated with CC starting with 50 mg/day on the day 2 of their cycle for 5 days, a transvaginal ultrasound will be done 1 week after the last pill, if all follicles are below 10 mm the dose will subsequently be increased to 100mg/day for 5 days then 150mg/day for 5 days if a transvaginal is done a week from the last pill and showed no response (all follicles being below 10 mm ).Maximum cc dose will be 150 mg (ASRM, 2013). Medroxyprogesterone (10 mg/d Provera for 10 days)will be given to induce withdrawal bleeding to start these steps again in a new cycle. These steps will be repeated for 3cycles before declaring the patient CC resistant.
- Response: Response to CC will be assessed by ovulation. TVS will be done by the same observer using a Samsung ultrasound machine, HS40.
A scan will be done 1 week after the last pill of each dose. No response: if all follicles are below 10 mm (ASRM, 2013), follicles >10mm, follow up till ovulation
| Study group | Role | What they receive |
|---|---|---|
| clomiphene citrate sensitive | Based on the ovulation pattern, these patients will be divided into two groups, one who ovulated with CC maximum 150 mg and others who did not ovulate considered as CC resistant. The patients who ovulated will be further classified into three subgroups based on whether they ovulated with 50 mg or 100 mg or 150 mg of CC.
The various parameters will be compared between the CC-resistant and CC-sensitive groups. Receives: Drug: Clomiphene Citrate | |
| clomiphene citrate resistent | Based on the ovulation pattern, these patients will be divided into two groups, one who ovulated with CC maximum 150 mg and others who did not ovulate considered as CC resistant. The patients who ovulated will be further classified into three subgroups based on whether they ovulated with 50 mg or 100 mg or 150 mg of CC.
The various parameters will be compared between the CC-resistant and CC-sensitive groups. Receives: Drug: Clomiphene Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
ovulation
follow up patient response to induction of ovulation by folliculometry till ovulation occurs
Measured: maximum 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study start1 Jan 2021
- Primary completion1 Mar 2022 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for PCOStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- Ain Shams Maternity Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alaa Sherif Zakaria Saad Elsewafy, Ain Shams Maternity Hospital
- Investigators
- Ahmed Rateb, professor, Study director, Ain Shams Maternity Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04887402
- Sponsor's protocol ID
- Parameters of resistence
- Status last verified
- Feb 2022
- First submitted
- 11 May 2021
- Last updated
- 16 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Atiomo WU, El-Mahdi E, Hardiman P. Familial associations in women with polycystic ovary syndrome. Fertil Steril. 2003 Jul;80(1):143-5. doi: 10.1016/s0015-0282(03)00502-8.
PubMed 12849816Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb;91(2):456-88. doi: 10.1016/j.fertnstert.2008.06.035. Epub 2008 Oct 23.
PubMed 18950759Misso ML, Wong JL, Teede HJ, Hart R, Rombauts L, Melder AM, Norman RJ, Costello MF. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012 May-Jun;18(3):301-12. doi: 10.1093/humupd/dms003. Epub 2012 Mar 19.
PubMed 22431566Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007 Aug 25;370(9588):685-97. doi: 10.1016/S0140-6736(07)61345-2.
PubMed 17720020Overbeek A, Kuijper EA, Hendriks ML, Blankenstein MA, Ketel IJ, Twisk JW, Hompes PG, Homburg R, Lambalk CB. Clomiphene citrate resistance in relation to follicle-stimulating hormone receptor Ser680Ser-polymorphism in polycystic ovary syndrome. Hum Reprod. 2009 Aug;24(8):2007-13. doi: 10.1093/humrep/dep114. Epub 2009 Apr 28.
PubMed 19401323Parsanezhad ME, Alborzi S, Zarei A, Dehbashi S, Omrani G. Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin. Int J Gynaecol Obstet. 2001 Oct;75(1):43-50. doi: 10.1016/s0020-7292(01)00470-2.
PubMed 11597618Radosh L. Drug treatments for polycystic ovary syndrome. Am Fam Physician. 2009 Apr 15;79(8):671-6.
PubMed 19405411Dunaif A, Fauser BC. Renaming PCOS--a two-state solution. J Clin Endocrinol Metab. 2013 Nov;98(11):4325-8. doi: 10.1210/jc.2013-2040. Epub 2013 Sep 5.
PubMed 24009134Sohrevardi SM, Nosouhi F, Hossein Khalilzade S, Kafaie P, Karimi-Zarchi M, Halvaei I, Mohsenzadeh M. Evaluating the effect of insulin sensitizers metformin and pioglitazone alone and in combination on women with polycystic ovary syndrome: An RCT. Int J Reprod Biomed. 2016 Dec;14(12):743-754.
PubMed 28331909WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004 Jan 10;363(9403):157-63. doi: 10.1016/S0140-6736(03)15268-3.
PubMed 1472617111. Wild, R.A., 2004. Ferriman Gallwey self-scoring: Performance assessment in women with the polycystic ovary syndrome (Doctoral dissertation, The University of Oklahoma Health Sciences Center).
Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril. 2013 Aug;100(2):341-8. doi: 10.1016/j.fertnstert.2013.05.033. Epub 2013 Jun 27.
PubMed 23809505
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Different Variables Predicting Ovulatory Response Among Clomiphene Citrate Resistance and Clomiphene Citrate Sensitive Patients With Polycystic Ovarian Syndrome.
- ClinicalTrials.gov ID
- NCT04887402
- Acronym / sponsor ID
- Parameters of resistence
- Conditions
- PCO, Induction of Ovulation, Clomiphene Citrate
- Keywords
- induction of ovulation by clomiphene citrate in PCO
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ain Shams Maternity HospitalUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 14 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Polycystic ovary syndrome (PCOS) is a common endocrinological disorder seen in 6%-10% of women (Human Reproduction, 2004). It is characterized by polycystic ovaries, anovulatory cycles, and hyperandrogenism.
In nearly 20% of infertile women, PCOS is said to be the key reason behind infertility (Norman et al., 2007).
PCOS is a syndrome that manifests variably from adolescence as oligomenorrhea or hirsutism or obesity and goes on to affect the reproductive performance of the female by causing anovulation. Some may even be severely affected by metabolic syndrome, diabetes mellitus, or endometrial carcinoma. It also increases the risk of ovarian and breast carcinoma (Atiomo et al., 2003).
PCOS falls in WHO type II anovulation (norm-gonadotropic norm-estrogenic anovulation) and is seen in 85% of anovulatory females. Although lifestyle modification is known to improve reproductive outcomes in females with PCOS, the gold standard treatment for norm-gonadotropic oligo/amenorrheic infertility (WHO Group II) was clomiphene citrate (CC) (Radosh L., 2009) until 2018, when ESHRE and ASRM have declared letrozole as the first-line treatment for ovulation induction (OI)( ESHRE 2018 guidelines).
To conclude, available data shows that letrozole is at least as effective as CC for ovulation and has comparable live birth rates. Importantly, it has definite advantages over CC. Many studies have shown letrozole to be as effective as gonadotropins, with added advantage of low cost and lower multiple pregnancy rates. However, the quality of medical evidence supporting aromatase inhibitors for OI, are inadequate, small in sample size, and inappropriate design. Moreover, there is very limited data on potential teratogenic effects, oocyte, embryo quality, and any effect on implantation. ( Misso et al., 2012) Those who fail to respond to CC are labeled as clomiphene resistant. It is common in approximately 15%-40% of women with PCOS (NICE, 2014). Major factors postulated for CC resistance include obesity, insulin resistance, (seen in nearly 50%-70% of females with PCOS) and hyperandrogenemia (Parsanezhad et al., 2001).Moreover, genetic predisposition is suggested to play a role in CC resistance (Overbeek et al., 2009).However, still, the current data available on the causes of CC resistance are not sufficient enough to direct our treatment.
It is seen in various studies (Sohrevardi et al.,2016) that the females who initially failed to respond to CC develop better ovulation and pregnancy outcomes on treatment with insulin-sensitizing agents. This indicates that insulin resistance may be a cause of CC resistance in females with PCOS. In fact, insulin-sensitizing agents (Azziz et al., 2009) decrease the dose of ovulation-inducing agent and time for follicular maturation in females with PCOS.
As of now, there have been no concrete studies to compare the metabolic profile of females who respond to CC and those who do not. It is still an enigma as to why some women respond to clomiphene, while others do not. By identifying the various factors which affect the response of CC in patients with infertility, a lot of time can be saved by giving alternate options of treatment to these patients. This study was done with the aim to analyze various clinical, metabolic, hormonal, and ultrasound parameters that might affect the response to clomiphene.
Detailed description
All PCO patients under the age of 40 who are subfertile with no identified cause but PCO will undergo the following;
- Detailed history taking including age, parity, medical, surgical history, previous trials of induction of ovulation.
- Physical examination:
- Vital data: blood pressure
- General examination: including weight in kilograms, and height in an upright posture without shoes using to the nearest 0.5 cm will be recorded. Body mass index (BMI) will be recorded from the above measurements. Waist circumference (WC) will be measured midway between the lower rib margin and the iliac crest in the mid-axillary line at the end of normal expiration. Hip circumference will be measured with the measuring tape at the highest prominence of the buttocks and parallel to the floor (Nishida et al., 2010). WC and hip circumference will be recorded after removing clothing from the area over the waist and hip.
The thyroid will be examined for any enlargement, nodules, or tenderness. The breast will be examined for any enlargement or galactorrhea. Signs of androgen excess will be looked for such as; excessive hair growth, acne, or alopecia. Excessive hair growth will be evaluated by modified Ferriman and Gallwey (Wild et al., 2004) (FG) score(<8 normal,8-15mild hirsutism,>15 moderate/severe hirsutism).
- Abdominal examination: including the presence of previous scars, uterine size, any tenderness, and presence of palpable masses, score on Ferriman Gallway scoring system.
- Pelvic examination: including uterine size, any adnexal mass, and tenderness, score on Ferriman Gallway scoring system.
- Investigation:
- Laboratory (on the 2nd day of cycle):
- Serum testosterone
- Androstenedione
- AMH
- LH
- FSH
- Fasting and 2hrs postprandial b) Imaging -Transvaginal ultrasound(on the 2nd day of cycle):
- Antral follicular count (AFC)
- Ovarian volume
- Endometrial thickness Will be done by the same observer using a Samsung ultrasound machine, HS40 (TVS probe frequency range 5-7 MHZ). The ovarian volume of each ovary will be assessed by ellipsoid formula, i.e., 0.52 × D1 (longitudinal) × D2 (oblique) × D3 (transverse) diameters. Mean ovarian volume will be calculated by adding the volume of both ovaries and then dividing it by 2. A note of ovarian follicles in each ovary will be also made and a total number of the follicles will be counted by scanning each ovary from the inner to the outer margin in longitudinal cross-section. Mean follicle number will be calculated by adding the follicles of both ovaries and then dividing it by 2.
- Method (stair step protocol):
All patients will be treated with CC starting with 50 mg/day on day 2 of their cycle for 5 days, a transvaginal ultrasound will be done 1 week after the last pill, if all follicles are below 10 mm the dose will subsequently be increased to 100mg/day for 5 days then 150mg/day for 5 days if a transvaginal is done a week from the last pill and showed no response (all follicles being below 10 mm ). The maximum cc dose will be 150 mg (ASRM, 2013). Medroxyprogesterone (10 mg/d Provera for 10 days)will be given to induce withdrawal bleeding to start these steps again in a new cycle. These steps will be repeated for 3cycles before declaring the patient CC resistant.
- Response: Response to CC will be assessed by ovulation. TVS will be done by the same observer using a Samsung ultrasound machine, HS40.
A scan will be done 1 week after the last pill of each dose. No response: if all follicles are below 10 mm (ASRM, 2013), follicles >10mm, follow up till ovulation Based on the ovulation pattern, these patients will be divided into two groups, one who ovulated with CC maximum 150 mg and others who did not ovulate considered as CC resistant. The patients who ovulated will be further classified into three subgroups based on whether they ovulated with 50 mg or 100 mg or 150 mg of CC.
The various parameters will be compared between the CC-resistant and CC-sensitive groups.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| clomiphene citrate sensitive | – | Drug: Clomiphene CitrateBased on the ovulation pattern, these patients will be divided into two groups, one who ovulated with CC maximum 150 mg and others who did not ovulate considered as CC resistant. The patients who ovulated will be further classified into three subgroups based on whether they ovulated with 50 mg or 100 mg or 150 mg of CC. The various parameters will be compared between the CC-resistant and CC-sensitive groups. |
| clomiphene citrate resistent | – | Drug: Clomiphene CitrateBased on the ovulation pattern, these patients will be divided into two groups, one who ovulated with CC maximum 150 mg and others who did not ovulate considered as CC resistant. The patients who ovulated will be further classified into three subgroups based on whether they ovulated with 50 mg or 100 mg or 150 mg of CC. The various parameters will be compared between the CC-resistant and CC-sensitive groups. |
Who may qualify
- Ages
- Up to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- The study will include 100 women with PCO Using PASS 11 program for sample size calculation and according to (sachdeva etal,2019), the expected frequency of PCOs patients with CC resistance = 54%, assuming that frequency in study population =54%+\- 10% and at 95% confidence level, sample size of 100 patients will be enough to detect this frequency.
Key inclusion criteria (3 listed)
- PCOS (based on Rotterdam's criteria: oligo/anovulation, hyperandrogenism clinical (hirsutism or less commonly male pattern alopecia) /biochemical (raised FAI or free testosterone) or polycystic ovaries on ultrasound(presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter, and/or increased ovarian volume (>10 ml)"1 . Unilaterality does not affect diagnosis; neither does the location of the cysts in the ovary.)
- Age <40 years.
- Semen analysis within normal according to WHO 2010.
Key exclusion criteria (7 listed)
- Women on any insulin-sensitizing agent.
- Women on lipid-lowering agent.
- Women with endocrinal disorder (such as thyroid dysfunction, insulin resistance(DM), and adrenal disorders).
- Women diagnosed with anorexia nervosa/bulimia nervosa.
- Women with hypothalamic or pituitary dysfunction.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clomiphene CitrateAll patients will be treated with CC starting with 50 mg/day on the day 2 of their cycle for 5 days, a transvaginal ultrasound will be done 1 week after the last pill, if all follicles are below 10 mm the dose will subsequently be increased to 100mg/day for 5 days then 150mg/day for 5 days if a transvaginal is done a week from the last pill and showed no response (all follicles being below 10 mm ).Maximum cc dose will be 150 mg (ASRM, 2013). Medroxyprogesterone (10 mg/d Provera for 10 days)will be given to induce withdrawal bleeding to start these steps again in a new cycle. These steps will be repeated for 3cycles before declaring the patient CC resistant. o Response: Response to CC will be assessed by ovulation. TVS will be done by the same observer using a Samsung ultrasound machine, HS40. A scan will be done 1 week after the last pill of each dose. No response: if all follicles are below 10 mm (ASRM, 2013), follicles >10mm, follow up till ovulation | Drug | clomiphene citrate resistent, clomiphene citrate sensitive |
Primary outcome
ovulation
Time frame: maximum 3 months
follow up patient response to induction of ovulation by folliculometry till ovulation occurs
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2022.
- Results publication: PubMed 12849816Atiomo WU, El-Mahdi E, Hardiman P. Familial associations in women with polycystic ovary syndrome. Fertil Steril. 2003 Jul;80(1):143-5. doi: 10.1016/s0015-0282(03)00502-8.
- Results publication: PubMed 18950759Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb;91(2):456-88. doi: 10.1016/j.fertnstert.2008.06.035. Epub 2008 Oct 23.
- Results publication: PubMed 22431566Misso ML, Wong JL, Teede HJ, Hart R, Rombauts L, Melder AM, Norman RJ, Costello MF. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012 May-Jun;18(3):301-12. doi: 10.1093/humupd/dms003. Epub 2012 Mar 19.
- Results publication: PubMed 17720020Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007 Aug 25;370(9588):685-97. doi: 10.1016/S0140-6736(07)61345-2.
- Results publication: PubMed 19401323Overbeek A, Kuijper EA, Hendriks ML, Blankenstein MA, Ketel IJ, Twisk JW, Hompes PG, Homburg R, Lambalk CB. Clomiphene citrate resistance in relation to follicle-stimulating hormone receptor Ser680Ser-polymorphism in polycystic ovary syndrome. Hum Reprod. 2009 Aug;24(8):2007-13. doi: 10.1093/humrep/dep114. Epub 2009 Apr 28.
- Results publication: PubMed 11597618Parsanezhad ME, Alborzi S, Zarei A, Dehbashi S, Omrani G. Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin. Int J Gynaecol Obstet. 2001 Oct;75(1):43-50. doi: 10.1016/s0020-7292(01)00470-2.
- Results publication: PubMed 19405411Radosh L. Drug treatments for polycystic ovary syndrome. Am Fam Physician. 2009 Apr 15;79(8):671-6.
- Results publication: PubMed 24009134Dunaif A, Fauser BC. Renaming PCOS--a two-state solution. J Clin Endocrinol Metab. 2013 Nov;98(11):4325-8. doi: 10.1210/jc.2013-2040. Epub 2013 Sep 5.
- Results publication: PubMed 28331909Sohrevardi SM, Nosouhi F, Hossein Khalilzade S, Kafaie P, Karimi-Zarchi M, Halvaei I, Mohsenzadeh M. Evaluating the effect of insulin sensitizers metformin and pioglitazone alone and in combination on women with polycystic ovary syndrome: An RCT. Int J Reprod Biomed. 2016 Dec;14(12):743-754.
- Results publication: PubMed 14726171WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004 Jan 10;363(9403):157-63. doi: 10.1016/S0140-6736(03)15268-3.
- Results publication11. Wild, R.A., 2004. Ferriman Gallwey self-scoring: Performance assessment in women with the polycystic ovary syndrome (Doctoral dissertation, The University of Oklahoma Health Sciences Center).
- Results publication: PubMed 23809505Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril. 2013 Aug;100(2):341-8. doi: 10.1016/j.fertnstert.2013.05.033. Epub 2013 Jun 27.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmed Rateb, professor study director
Ain Shams Maternity Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PCO and Induction of Ovulation, run by Ain Shams Maternity Hospital at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alaa Sherif Elsewafy, Master (01114860044 ext. 002, dr_2laa_sherif@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ovulation (time frame: maximum 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04887402, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2022.