Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination

Background Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women in the reproductive age group, and is one of the most common causes of hyperandrogenic anovulatory infertility. The aromatase inhibitor, letrozole, has been used for induction of ovulation. The purpose of this study was to compare the effects of letrozole and clomiphene citrate in induction of ovulation among patients with PCOS undergoing intrauterine insemination. Methods In a double-blind randomized study, 60 infertile patients with PCOS received standard doses of either clomiphene citrate or letrozole as an induction protocol prior to intrauterine insemination. A hormonal profile, pelvic ultrasound, hysterosalpingogram, and/ or laparoscopy were done for all patients. The patients were monitored for ovulation by translational ultrasonographic folliculometry, with measurement of number and size of the follicles, as well as endometrial thickness. Human chorionic gonadotrophin (HCG) was injected intramuscularly when at least one mature follicle > 18 mm diameter was detected, and intrauterine insemination was performed 32-36 hours later. Transvaginal ultrasound and β-HCG measurement were performed for confirmation of pregnancy. Results Letrozole and clomiphene citrate achieved follicle maturation within a mean ± standard deviation (SD) of 13.2 ± 1.53 and 14.1 ± 1.35 days, respectively, showing no significant difference (P > 0.05). The mean number of follicles reaching >18 mm on the day of HCG administration was significantly higher in patients who received clomiphene citrate (2.9 ± 1.77) than in those receiving letrozole (1.2 ± 0.9). Letrozole had a significantly greater effect than clomiphene citrate on endometrial thickness (9.16 ± 1.36 versus 4.46 ± 1.71). The number of pregnancies achieved in the letrozole group was significantly (P < 0.05) greater than in the clomiphene group. Conclusion Letrozole in patients with PCOS is as effective as clomiphene citrate in inducing ovulation, and although the number of follicles produced by induction with letrozole were less than those produced by clomiphene, letrozole had a significantly greater effect on endometrial thickness than clomiphene citrate, and the incidence of pregnancy after intrauterine insemination was significantly higher, with a lower incidence of multiple pregnancy.

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Effects of Letrozole-HMG and Clomiphene-HMG on Incidence of Luteinized Unruptured Follicle Syndrome in Infertile Women Undergoing Induction Ovulation and Intrauterine Insemination: A Randomised Trial

Global Journal of Health Science ◽

10.5539/gjhs.v8n4p244 ◽

2015 ◽

Vol 8 (4) ◽

pp. 244 ◽

Cited By ~ 3

Author(s):

Azra Azmoodeh ◽

Mansoureh Pejman Manesh ◽

Firouzeh Akbari Asbagh ◽

Azizeh Ghaseminejad ◽

Zeinab Hamzehgardeshi

Keyword(s):

Menstrual Cycle ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Clomiphene Citrate ◽

Randomised Trial ◽

Induction Of Ovulation ◽

Infertile Women ◽

Significant Difference ◽

Preovulatory Follicles ◽

Luteinized Unruptured Follicle

BACKGROUND: Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes. METHODS: The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18–23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38–40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome. RESULTS: There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p < 0.001). The results of our multivariate logistic regression indicate that size 18–19.9 mm leads to the complete LUF less than ≥22 mm [AOR: 0.25, P = 0.005], and in size 20– 21.9 mm as well [AOR: 0.17, P = 0.002]. CONCLUSION: Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.

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Effects of Letrozole in Prevention of Premature Luteinizing Hormone (LH) Surge in Infertile Women with Clomiphene Citrate Resistant Polycystic Ovary Syndrome (PCOS) Undergoing Intrauterine Insemination

Galen Medical Journal ◽

10.31661/gmj.v4i3.232 ◽

2015 ◽

Vol 4 (3) ◽

pp. 104-11

Author(s):

Afsoon Zarei ◽

Tahere Bahrami Shabahrami ◽

Nasrin Dadras

Keyword(s):

Luteinizing Hormone ◽

Pregnancy Rate ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Clomiphene Citrate ◽

Control Group ◽

Lh Surge ◽

Significant Difference ◽

Premature Lh Surge

Background: Polycystic ovarian syndrome (PCOS) is among the important causes of infertility in young women. Premature luteinizing hormone (LH) surge (PLS) is one of its complications. PLS can reduce the quality of oocytes and therefore decrease the success of intrauterine insemination (IUI). Letrozole, a non-steroidal aromatase inhibitor, prevents LH surge. In this study, we aim to evaluate the effects of letrozole on preventing premature LH surge in clomiphene-resistant patients with PCOS undergoing IUI. Materials and Methods: In this randomized clinical trial, 131 patients who were developed with PCOS were selected for IUI cycle, divided into two groups randomly: control group (n=67) and letrozole group (n=64). Incidence of premature LH surge, pregnancy, abortion and ongoing pregnancy rate, endometrial thickness and number of follicles were measured in both groups. Results: No significant difference was seen between mean ages in the two groups; 11.9% of the control group and 21.9% of the letrozole group became pregnant (P =0.005); furthermore, premature LH surge was seen in 4.7% of the letrozole group and 8.9% of the control group (P =0.003). E2 and Endometrial thickness was higher in letrozole group; however, LH was significantly higher in the control group (P =0.026). Conclusion: Administration of letrozole in clomiphene-resistant patients with PCO undergoing IUI cycle can decrease the incidence of PLS. In addition, it can increase pregnancy rate significantly. Therefore, using letrozole is more reasonable in patients who have not responded to clomiphene or are hypersensitive. [GMJ.2015;4(3):104-11]

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Step-up protocol gonadotrophin versus laparoscopic ovarian drilling in clomiphene citrate resistant PCOS infertile women in two Iraqi hospitals

AL-Kindy College Medical Journal ◽

10.47723/kcmj.v15i1.89 ◽

2019 ◽

Vol 15 (1) ◽

pp. 103-109

Author(s):

Thikra N Abdull

Keyword(s):

Pregnancy Rate ◽

Polycystic Ovarian Syndrome ◽

Polycystic Ovary ◽

Transvaginal Ultrasound ◽

Clomiphene Citrate ◽

Multiple Pregnancy ◽

Reproductive Age ◽

Infertile Women ◽

Laparoscopic Ovarian Drilling ◽

Ovarian Syndrome

Background: Polycystic ovarian syndrome is a common endocrine disorder affecting 6-10% of women of reproductive age and the most common cause of anovulatory infertility. Objective: The aim of the study was to compare the effectiveness, side effects and outcomes of step-up gonadotrophin protocol versus laparoscopic ovarian diathermy (LOD) in infertile patients with clomiphene citrate resistant polycystic ovary syndrome. Methods: The sample included women who attended our infertility clinic at Al-Elwiya Maternity Teaching Hospital and Kamal Al-Samarraee for Infertility and IVF Hospital in Baghdad/ Iraq from November 2013 to November 2014. Eighty cases of infertile women with polycystic ovarian syndrome who failed to ovulate with clomiphene citrate for six months where collected, forty women treated with step-up protocol with low dose recombinant FSH gonadotrophin which increased gradually according to ovulation response, another forty women treated with LOD. Ovulation monitoring in each group was done with transvaginal ultrasound to exclude monofollicullar, bifollicular ovulation, ovarian hyperstimulation syndrome, multiple pregnancy and pregnancy rate in each cycle for 6 cycles. Results: Higher unifollicular ovulation and pregnancy rate in LOD than step-up protocol (91.4% & 25% versus 75% & 10%) respectively, while multifollicular and hyperstimulation rate were higher in gonadotrophin group (24.3% & 0.1% versus 8.50% & nil) respectively. Conclusion: Ovulation induction and pregnancy rate per cycle was higher with LOD group, not time consuming, also there was no risk of hyperstimulation of the ovary or twin pregnancy as compared to the step-up protocol with gonadotrophin

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Study of endometrial thickness and pregnancy outcome following induction of ovulation and intrauterine insemination in primary infertility

Indian Journal of Medical Sciences ◽

10.25259/ijms_13_2020 ◽

2020 ◽

Vol 71 ◽

pp. 118-122

Author(s):

Sweta Nathani ◽

Pallab Kumar Mistri

Keyword(s):

Prospective Observational Study ◽

Primary Outcome ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Transvaginal Ultrasound ◽

Standard Procedure ◽

Clomiphene Citrate ◽

Significant Difference ◽

Group A ◽

Transvaginal Ultrasound Scan

Objective: Infertility affects approximately 10–15% of couples. Assessment of the endometrium with ultrasound has become a standard procedure during the diagnostic workup and treatment of infertility. Our study was designed to investigate whether endometrial thickness on the day of human chorionic gonadotropin administration is a predictor of intrauterine insemination (IUI) success as the primary outcome. Materials and Methods: In the prospective observational study, a serial transvaginal ultrasound scan was performed to measure endometrial thickness following ovulation induction with clomiphene citrate and IUI. One hundred and nine IUI cycles were chosen and the outcome was measured in terms of whether pregnancy occurred or not. Results: There was a statistically significant difference (P = 0.001) between the two groups with respect to mean endometrial thickness (mm). It was also seen significantly higher numbers of pregnancy in Group A (endometrial thickness ≥ 7 mm). Conclusion: The present study identified a statistically significant difference in mean endometrial thickness between cycles that resulted in pregnancy and those did not. Consequently, clinicians providing IUI for infertile couples must pay close attention to endometrial development.

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Extended Letrozole Versus Recombinant FSH in Ovulation Induction in Cases of Clomiphene Citrate Resistant Polycystic Ovary

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i1931076 ◽

2021 ◽

pp. 31-39

Author(s):

Nehad Maher Motit ◽

Ayman Abdelaziz El-Dorf ◽

Shahinaz Hamdy Elshourbagy ◽

Manal Mostafa Abdullah

Keyword(s):

Ovulation Induction ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

Multiple Pregnancy ◽

Recombinant Fsh ◽

Dominant Follicle ◽

Significance Level ◽

Significant Difference ◽

Insignificant Difference

Background: Clomiphene citrate (CC) is still the traditional therapy used for inducing ovulation in polycystic ovary syndrome (PCOS). Clomiphene resistance, which refers to persistence of anovulation after standard CC therapy, occurs in 15%–20% of patients. We aimed to compare between extended letrozole versus recombinant FSH in ovulation induction in cases of clomiphene resistant polycystic ovary Methods: Seventy women with PCOS were included then patients were equally randomized to receive one of the two drugs to be given over the next 3 months. In current study Group A: letrozole group 2.5 mg two tablets once daily for 10 days from day 2 of menses. Group B: Recombinant FSH 75 i.u s.c daily from day 2 for 5 days then monitoring dose according to folliculometry. Results: There was non-significant difference between two groups as regard FSH and LH but as regard Serum E2 (pg/mL) at day 5 of HCG administration there was significant higher in FSH recombinant group. There was insignificant difference between two groups as regard Ovulating, Number of follicles >18. There was insignificant difference between two groups as regard Size of dominant follicle, endometrial thickness at hCG (mm). OHSS, discontinuation due to OHSS, clinical pregnancy, multiple pregnancy and abortion was higher in FSH recombinant group but differences didn’t reach significance. Conclusions: There was non-significant difference between two groups in relation to ovulation, Number of follicles, Size of dominant follicle, Endometrial thickness at day of HCG injection however it was reported that OHSS, discontinuation due to OHSS, positive pregnancy test, was higher in FSH recombinant group but differences didn’t reach significance level.

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A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome

Medical Sciences ◽

10.3390/medsci7090095 ◽

2019 ◽

Vol 7 (9) ◽

pp. 95 ◽

Cited By ~ 2

Author(s):

Michael Costello ◽

Rhonda Garad ◽

Roger Hart ◽

Hayden Homer ◽

Louise Johnson ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Ovulation Induction ◽

Polycystic Ovary ◽

Clomiphene Citrate ◽

Multiple Pregnancy ◽

Reproductive Age ◽

Supporting Evidence ◽

First Line ◽

Ovary Syndrome ◽

Ultrasound Monitoring

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Lifestyle change is considered the first line treatment for the management of infertile anovulatory women with PCOS, and weight loss for those who are overweight or obese. First line medical ovulation induction therapy to improve fertility outcomes is letrozole, whilst other less efficacious ovulation induction agents, such as clomiphene citrate, metformin, and metformin combined with clomiphene citrate, may also be considered. Metformin combined with clomiphene citrate is more effective than clomiphene citrate alone. In obese women with PCOS, clomiphene citrate could be used in preference to metformin alone whilst clomiphene citrate could be added to metformin alone in order to improve reproductive outcome in all women with PCOS. Gonadotrophins, which are more effective than clomiphene citrate in therapy naïve women with PCOS, can be considered a first line therapy in the presence of ultrasound monitoring, following counselling on the cost and the potential risk of multiple pregnancy.

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Clomiphene Citrate or Letrozole for Ovulation Induction in Women with Polycystic Ovarian Syndrome: A Prospective Randomized Trial

Journal of SAFOG with DVD ◽

10.5005/jp-journals-10006-1091 ◽

2010 ◽

Vol 2 (2) ◽

pp. 169-173

Author(s):

Randhir Puri ◽

Ahmed Badawy ◽

Ibrahim Abdel Aal ◽

Mohamed Abulatta

Keyword(s):

Randomized Trial ◽

Ovulation Induction ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

University Teaching ◽

Prospective Randomized Trial ◽

Serum Estradiol ◽

Serum Progesterone ◽

Significant Difference

Objective To compare the effects of letrozole (5 mg) and clomiphene citrate (100 mg) for ovulation induction in women with polycystic ovary syndrome (PCOS). Design Prospective randomized trial. Setting University teaching hospital and private practice setting. Patients The study comprised a total of 438 infertile women (1063 cycles) with PCOS. Intervention Patients were randomized to treatment with 5 mg of letrozole daily (218 patients, 545 cycles) or 100 mg of clomiphene citrate daily (220 patients, 518 cycles) for 5 days starting on day 3 of menses. Timed intercourse was advised 24 to 36 hours after hCG injection. Main Outcome Measure Number of follicles, serum estradiol, serum progesterone, endometrial thickness, and pregnancy and miscarriage rates. Results The mean age, parity, and duration of infertility in both groups were similar. The total number of follicles was statistically significantly greater in the clomiphene citrate group (6.8 _ 0.3 vs 4.4 _ 0.4). Endometrial thickness at the time of hCG administration was statistically significantly greater in the CC group (9.2 _ 0.7 mm vs 8.1 _ 0.2 mm). The duration to reach a dominant follicle was statistically significantly longer in the letrozole group (12.1_1.3 vs 8.8_2.9 days). Ovulation occurred in 365 out of 540 cycles (67.5%) in letrozole group and 371 out of 523 cycles (70.9%) without a statistically significant difference. Levels of serum estradiol and progesterone were statistically significantly higher in the clomiphene citrate group. The pregnancy rate per cycle was 15.1% in the letrozole group and 17.9% in the clomiphene citrate group without statistically difference between the groups. Conclusion The results of this study did not show any advantage to the use of letrozole over clomiphene citrate as a first-line treatment for induction of ovulation in women with PCOS (Fertil Steril_2009;92:849-52. _2009 by American Society for Reproductive Medicine).

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Comparison of the efficiency of clomiphene citrate and letrozole in combination with metformin in moderately obese clomiphene citrate - resistant polycystic ovarian syndrome patients

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1604146b ◽

2016 ◽

Vol 144 (3-4) ◽

pp. 146-150 ◽

Cited By ~ 3

Author(s):

Artur Bjelica ◽

Aleksandra Trninic-Pjevic ◽

Ljiljana Mladenovic-Segedi ◽

Nenad Cetkovic ◽

Djordje Petrovic

Keyword(s):

Retrospective Study ◽

Polycystic Ovary Syndrome ◽

Pregnancy Rate ◽

Polycystic Ovary ◽

Intrauterine Insemination ◽

Clomiphene Citrate ◽

Obese Patients ◽

Ovary Syndrome ◽

Metformin Therapy ◽

Significant Difference

Introduction. Polycystic ovary syndrome is the most common endocrinopathy in women of reproductiveage. Therapy for those who want to get pregnant involves ovulation induction using clomiphene citrate, metformin, letrozole and gonadotropins. Objective. The aim of the study was to compare the efficacy of combinations of clomiphene citrate-metformin and letrozole-metformin in obese patients who are resistant to clomiphene citrate alone. Methods. The investigation was conducted as a retrospective study involving 60 moderately obese patients with polycystic ovary syndrome. Thirty-one of them received the clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was carried out for the procedures of intrauterine insemination (IUI). Results. The age of patients, duration of infertility, and body mass index in both groups were similar. There was statistically significant difference in the thickness of the endometrium in favor of the group having the letrozole-metformin therapy (8.9 ? 1.7 mm) compared with the group receiving the clomiphene citrate-metformin treatment (6.3 ? 1.3 mm). The number of follicles was not statistically significantly different. Pregnancy rate in the first cycle of IUI in the clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also was not statistically different. After the third IUI cycle, the pregnancy rate was significantly higher in the letrozole group (20.6%), while in the clomiphene citrate group it was (9.6%). Conclusion. This retrospective study demonstrated the advantages of the use of letrozole over clomiphene citrate in combination with metformin in moderately obese patients with polycystic ovary syndrome who are resistant to stimulation with clomiphene citrate alone.

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Endometrial and follicular development following stair-step and traditional protocols in women with polycystic ovary syndrome: An RCT

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v19i6.9375 ◽

2021 ◽

Author(s):

Sholeh Shahgheibi ◽

Fariba Seyedoshohadaei ◽

Danial Khezri ◽

Solmaz Ghasemi

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Endometrial Thickness ◽

Clomiphene Citrate ◽

Ovarian Follicles ◽

Left Ovary ◽

Ovulation Rate ◽

Control Group ◽

Ovary Syndrome ◽

Significant Difference

Background: Various strategies have been proposed for polycystic ovary syndrome (PCOS) treatment. Objective: To investigate and compare the number and size of ovarian follicles, endometrial thickness, and ovulation rate by traditional protocol (TP) and stair-step protocol (SSP). Materials and Methods: Sixty infertile PCOS women were allocated into two groups (SSP = 30 and control TP = 30) between May and October 2019 in the Besat Hospital, Sanandaj, Iran. In the SSP group, the infertile women were treated with 50 mg/daily clomiphene citrate (CC) for five days, while the nonresponsive women were prescribed 100 mg daily CC for five days in the same cycle. The maximum dose (150 mg) was administered until ovulation occurred. In the control group, in non-ovulatory cases, the dose was increased in the next cycle. Ultrasound was used to detect ovulation. Results: Endometrial thickness changes with various doses of CC were significantly different in the TP. The comparison of both protocols showed a significant difference in endometrial thickness only at 50 mg CC. The number of follicles in the left ovary was significantly different in both protocols at 150-mg CC. The size of ovarian follicles in the left ovary was significantly different between the two protocols at 100-mg CC. The ovulation rate was significantly different in the SSP at 100- and 150-mg doses of CC. Moreover, 86% of ovulation occurred at 100-mg CC in the SSP, while this rate was 73% in the TP. Conclusion: The most appropriate dose for ovulation in patients with PCOS is 100 mg CC. Key words: Polycystic ovary syndrome, Clomiphene, Infertility, Ovulation induction.

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Role of intrauterine tubo-peritoneal insemination and intrauterine insemination in the treatment of infertility

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20171842 ◽

2017 ◽

Vol 5 (5) ◽

pp. 2057

Author(s):

Disha Gupta ◽

Asha Verma ◽

Richa Gupta ◽

Soniya Saini ◽

Anuradha Salvi ◽

...

Keyword(s):

Pregnancy Rate ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Clomiphene Citrate ◽

Positive Outcome ◽

Exclusion Criteria ◽

Significant Difference ◽

Infertile Patients ◽

Urine Pregnancy Test

Background: Infertility management has become more substantial and relevant with an increase in the number of infertile patients as well as advances in the science of reproduction. The objective of our study was to assess the role of intrauterine tuboperitoneal insemination (IUTPI) and intrauterine insemination (IUI) in the treatment of infertile patients.Methods: 236 infertile patients, 118 in each group attending the infertility clinic, after applying both inclusion and exclusion criteria were enrolled in the present study. Patients in each study group were given clomiphene citrate for ovarian stimulation followed by injection hCG for triggering ovulation. Insemination with washed husband’s sperm was performed about 36-40 hours after hCG administration, using 10ml of inseminate in IUTPI and 0.5ml inseminate in IUI. The patient was then called after 2 weeks for urine pregnancy test (UPT) which, if positive was considered as clinical pregnancy.Results: Out of the total 236 cases, 42 cases had a positive outcome. Out of these 42 positive cases, 27 were from IUTPI group whereas 15 from IUI group. The pregnancy rate was 22.88% in IUTPI and 12.71% in IUI (p=0.039), which was a statistically significant difference. Endometrial thickness, preovulatory follicle number and prewash sperm motility significantly affected positive outcome in IUTPI. Factors like patient’s age, BMI<25, bilateral patent tubes and decreased duration of infertility also positively affected the treatment outcome.Conclusions: Our study found IUTPI to have better pregnancy rate compared to IUI. IUTPI may become a first line option for treatment of infertile patients.

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