| Table 1. Characteristics of the included studies. LE=letrozole; CC=clomiphene citrate; n= number. | |||||||
| Author (year) | Country | Intervention | Method of Conception | Ovulation triggering and hCG use | Patients (n) |
Cycles (n) |
Outcomes included in the meta-analysis |
|---|---|---|---|---|---|---|---|
| Ahmed Abdalla et al. ( |
Egypt | -LE: 5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | LE: 35(95%) received hCG 10.000UI (IM) when at least one follicle >18mm CC: 24(80%) received hCG 10.000UI (IM) when at least one follicle >18mm *Both patients’ groups were advised to have intercourse 24 to 36 hours after hCG injection |
LE: 40 CC: 40 |
LE:120 CC:120 |
Pregnancy rate Ovulation rate |
| Al-Obaidi et al. ( |
Iraq | -LE: 2.5mg 2x/day for 5 days (3rd-7th day of the cycle) -CC: 50mg 2x/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | Both groups received hCG subcutaneously, when at least one follicle >18mm, to trigger ovulation | LE: 40 CC: 40 |
N/R | ovulation rate |
| Iraq | -LE: 2,5 - 7,5 mg (stair-step pattern) for 5 days (2nd-6th day) -CC: 50 - 150 mg*(stair-step pattern) for 5 days (2nd-6th day) |
Timed sexual intercourse | Both groups received hCG, when at least one follicle >18mm, to trigger ovulation | LE: 50 CC: 50 |
LE: 150 CC: 150 |
Pregnancy rate Ovulation rate |
|
| Amer et al. (2017) |
United Kingdom |
-LE: 2,5 - 5 mg/day* (increased in the next cycle in non-responders) starting on days 2-4 of the cycle -CC: 50-100 mg* |
Timed sexual intercourse | Ovulation was diagnosed with a progesterone level of ≥25 nmol/l, a follicle diameter ≥17 mm, and/or occurrence of pregnancy. Cycles were initially monitored with ultrasound follicle tracking. The study does not explicitly state the administration of exogenous hCG as a trigger. | LE: 80 CC: 79 |
LE: 320 CC: 474 |
Pregnancy rate ovulation rate live birth rate miscarriage rate multiple pregnancy rate |
| Ashfaq et al. (2018) |
Pakistan | -LE: 5 mg/day for 5 days -CC: 100 mg/day for 5 days |
did not mention timed intercourse or IUI | Induction of ovulation is assessed by TVS. If follicle of >2cm is found on 12 days TVS and smaller/collapsed on 16 days TVS, ovulation induction was labeled. | LE: 40 CC: 40 |
N/R | ovulation rate |
| Atay et al. (2006) |
Turkey | -LE: 2,5 mg for 5 days (3rd-7th day) -CC: 100 mg/day for 5 days (3rd-7th day |
Timed sexual intercourse | Both groups received hCG 10.000UI subcutaneously (SC), when at least one follicle ≥ 18 mm, to trigger ovulation | LE: 51 CC: 55 |
LE: 51 CC: 55 |
Pregnancy rate ovulation rate multiple pregnancy rate |
| India | -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
did not mention timed intercourse or IUI | A single injection of 10,000 IU hCG was given, if at least one follicle attained 18 mm. | LE: 69 CC:78 |
LE:132 CC:156 |
Pregnancy rate ovulation rate |
|
| Bansal et al. (2021) |
India | -LE: 2,5 - 7,5 mg/day for 5 days (2nd-6th day) the dose was increased by 2.5mg every cycle -CC: 50-150 mg/day for 5 days (2nd-6th day) the dose was increased by 50 mg every cycle |
Timed sexual intercourse | When the size of the dominant follicle reached >18 mm, human Chorionic Gonadotrophin (hCG) 5000 IU was given as a trigger intramuscularly for ovulation. | LE: 45 CC:45 |
LE: 135 CC:135 |
Pregnancy rate ovulation rate |
| Basarakod et al. ( |
India | -LE: 2,5-7,5mg/day for 5 days (2nd-6th day) (stepwise increase in dose up to 7.5mg in the next cycle in the absence of ovulation) -CC: 50 - 150 mg for 5 days (2nd-6th day) |
Timed sexual intercourse | When a matured follicle of size 18-22 mm was noted, ovulation trigger using HCG 10000IU injection IM was given | LE: 40 CC: 40 |
LE: 80 CC:104 |
Pregnancy rate ovulation rate |
| Bayar et al. (2006) |
Turkey | -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | Human chorionic gonadotropin (hCG) 10,000 IU, SC, was administered to trigger ovulation when at least one mature follicle (≥18 mm) developed. |
LE: 38 CC: 36 |
LE: 99 CC: 95 |
Pregnancy rate ovulation rate miscarriage rate |
| Begum et al. (2009) |
Bangladesh | -LE: 7,5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 150 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | A single injection of 10,000 IU hCG was given if at least one follicle attained 18 mm. Ovulation was ascertained by observing rupture of the follicle by ultrasonogram (USG) and day 21 serum P level (≥10ng/mL was considered ovulatory). | LE: 32 CC: 32 |
LE: 64 CC: 64 |
Pregnancy rate ovulation rate miscarriage rate multiple pregnancy rate |
| Behnoud et al. (2019) |
Iran | -LE: 5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | hCG was prescribed for LH surge if there was 1 or more than one dominant follicle with triple line endometrial pattern. | LE: 40 CC: 40 |
N/R | Pregnancy rate |
| Chakravorty et al. ( |
India | -LE: 2,5 - 5 mg* for 5 days (3rd-7th day of the cycle) -CC: 50-150 mg* for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | When at least one mature follicle (mean diameter ≥18mm) was observed, 10,000IU of human chorionic gonadotropin (hCG) were given subcutaneously to trigger ovulation. |
LE: 66 CC: 61 |
LE: 198 CC: 183 |
Pregnancy rate ovulation rate |
| Dehbashi et al. (2009) |
Iran | -LE: 5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | Intramuscular hCG (10,000IU) was administered to trigger ovulation when at least one mature follicle (≥18mm) was developed. | LE: 50 CC: 50 |
N/R | Pregnancy rate ovulation rate live birth rate miscarriage rate multiple pregnancy rate |
| Ghahiri et al. (2016) |
Iran | -LE: 5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | Ovulation confirmation relied on calendar, history-taking, and pregnancy occurrence. In case of delayed menstruation in a patient who had ovulated, β-HCG was measured to confirm pregnancy. | LE: 50 CC: 51 |
N/R | Pregnancy rate ovulation rate miscarriage rate multiple pregnancy rate |
| Hasnat et al. (2023) |
Bangladesh | -LE: 2,5 - 7,5 mg/day for 5 days (2nd-6th day) the dose was increased by 2.5mg every cycle -CC: 50-150 mg/day for 5 days (2nd-6th day) the dose was increased by 50 mg every cycle |
Timed sexual intercourse | Once the dominant follicle surpassed 18mm in size, ovulation was induced by administering 5000IU of hCG intramuscularly. | LE: 51 CC: 51 |
LE: 102 CC: 102 |
Pregnancy rate ovulation rate |
| Hegde & Maitra (2020) |
India | -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | hCG was administered at a dose of 5000 IU when at least 1 mature follicle (18-22mm) was detected. | LE: 25 CC: 25 |
LE: 25 CC: 25 |
Pregnancy rate ovulation rate multiple pregnancy rate |
| Hendawy et al. ( |
Egypt | -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
Intrauterine insemination (IUI) was performed 32-36 hours after hCG. A single insemination was performed. Semen specimens were prepared using Ham’s F-10 medium with L-glutamine, washed, and kept at room temperature for 45 minutes until transfer into the uterine cavity using a Wallace intrauterine insemination catheter. Time interval between semen production and transfer did not exceed 2.5 hours. | HCG 10,000 IU was given intramuscularly to trigger ovulation when at least one mature follicle ≥18mm diameter was detected. Luteal Phase Support: Progesterone vaginal pessaries 400 mg once daily for 15 days. |
LE: 30 CC: 30 |
N/R | Pregnancy rate multiple pregnancy rate |
| Hussain et al. ( |
Malaysia | -LE: 5 mg/day for 5 days (5th-9th day of the cycle) -CC: 100 mg/day for 5 days (5th-9th day of the cycle) |
did not mention timed intercourse or IUI | Ovulation was diagnosed when the mature dominant follicle (DF) was approximately 18 to 22mm, followed by evidence of rupture approximately 3 to 4 days later, observed via serial transvaginal ultrasound (TVS). hCG use was not mentioned. |
LE: 75 CC: 75 |
LE: 75 CC: 75 |
Pregnancy rate ovulation rate |
| Hussein et al. ( |
Iraq | -LE: 5 mg/day for 5 days (5th-9th day of the cycle) -CC: 100 mg/day for 5 days (5th-9th day of the cycle) |
Timed sexual intercourse | Recombinant hCG was administered subcutaneously to trigger ovulation when at least one mature follicle 18 mm diameter was detected. | LE: 40 CC: 40 |
LE: 40 CC: 40 |
Pregnancy rate |
| India | -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) the dose was increased in non-responders up to 7.5mg/day in the next cycle -CC: 50mg/day for 5 days (3rd-7th day of the cycle) the dose was increased in non-responders up to 150 mg in the next cycle |
Timed intercourse/intrauterine insemination (IUI) as appropriate. The article does not explicitly state the exact number of patients who underwent IUI neither the methods | An injection of 5,000 to 10,000 IU of human chorionic gonadotropin (hCG) was administere | LE: 192 CC: 192 |
LE: 192 CC: 192 |
Pregnancy rate ovulation rate live birth rate miscarriage rate |
|
| India | -LE: 5 mg/day for 5 days (2nd-6th day) -CC: 100 mg/day for 5 days (2nd-6th day) |
Timed intercourse or Intrauterine Insemination (IUI) was advised. The choice between both was made “as per the patient requirement” | A single injection of 10,000 IU of hCG was administered, if at least one follicle attained 17-18 mm diameter during follicular monitoring. Luteal Support: Duphastone 10 mg daily was given to all patients. |
LE: 52 CC: 51 |
LE: 52 CC: 51 |
Pregnancy rate ovulation rate live birth rate miscarriage rate multiple pregnancy rate |
|
| Khakwani et al. ( |
Pakistan | LE: 5 mg/day for 5 days (3rd-7th day of the cycle) CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
did not mention timed intercourse or IUI | All women underwent transvaginal scan (TVS) for the evaluation of ovulation induction. If follicle of more than 2 cm was located on 12 day on TVS and/or small/collapsed on 16 day on TVS, ovulation induction was considered yes or otherwise. | LE: 36 CC: 34 |
N/R | ovulation rate |
| Legro et al. (2014) |
United States |
After spontaneous menses or withdrawal bleeding induced by progestin administration progesterone acetate: -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) the dose was increased in non-responders up to 7.5mg/day in the next cycle (stepwise increase dose) -CC: 50 mg/day for 5 days (3rd-7th day of the cycle) the dose was increased in non-responders up to 150 mg in the next cycle |
Timed intercourse and Intrauterine Insemination (IUI) | Ovulation predictor kits were not used. |
LE: 301 CC: 308 |
LE:1352 CC:1425 |
Pregnancy rate ovulation rate live birth rate miscarriage rate multiple pregnancy rate |
| Mohamed et al. ( |
Egypt | -LE: 5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
did not mention timed intercourse or IUI | If a dominant follicle (DF) was present (DF > 12 mm), a repeat TVS was performed every 2 days. Ovulation was diagnosed when the mature DF was approximately 18 to 22 mm followed by evidence of rupture approximately 3 to 4 days later. If a dominant follicle (DF) was absent (DF < 12 mm), a repeat TVS was performed every 3 - 4 days later. |
LE: 50 CC: 50 |
LE: 152 CC: 156 |
Pregnancy rate ovulation rate |
| Nambiar (2019) |
India | Controlled ovarian hyperstimulation (COH): -LE: 5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 100 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | A single injection of hCG 10,000 IU IM was given if at least one follicle was >14 mm and the endometrial thickness at least more than 8 cm. A second TVS was done after 48 hours of hCG to observe the release of the egg. |
LE: 104 CC: 96 |
N/R | Pregnancy rate ovulation rate miscarriage rate |
| Nazmashamim et al. ( |
India | LE: 5 mg/day for 5 days (2nd-6th day) CC: 100 mg/day for 5 days (2nd-6th day) |
did not mention timed intercourse or IUI | hCG 5000 IU was administered within 24 hrs after the appearance of the dominant follicle | LE: 32 CC: 31 |
N/R | Pregnancy rate ovulation rate |
| India | -LE: 2,5mg/day for 5 days (3rd-7th of the cycle). The dose would be increased up to 5mg/day in the next cycle in non-responders -CC: 50mg /day for 5 days (3rd-7th day of the cycle). The dose would be increased up to 100mg/day in non-responders |
Timed sexual intercourse | Injection hCG 10,000 IU intramuscularly was given to the patients when a dominant follicle ≥18 mm and ET ≥6 mm was observed. | LE: 98 CC: 106 |
LE: 94 CC: 18 |
Pregnancy rate ovulation rate live birth rate miscarriage rate |
|
| Sharief & Nafee ( |
Iraq | -LE: 2,5 - 5 mg* for 5 days (3rd-7th day of the cycle) -CC: 100 - 200 mg* for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | When at least one mature follicle (mean diameter >18 mm) was observed, 10.000IU of human chorionic gonadotropin (HCG) was given subcutaneously to trigger ovulation. | LE: 120 CC: 119 |
N/R | Pregnancy rate ovulation rate |
| Wang et al. ( |
China | -LE: 2,5 mg/day for 5 days (3rd-7th day of the cycle) -CC: 50 mg/day for 5 days (3rd-7th day of the cycle) |
Timed sexual intercourse | When at least one dominant follicle reached 18mm in diameter, human chorionic gonadotropin (hCG) at a dose of 8000 or 10,000IU was given intramuscular to trigger ovulation. | LE: 120 CC: 119 |
N/R | Pregnancy rate ovulation rate |
| Wang et al. ( |
China | -LE: 2,5 mg/day for 5 days (5th-9th day of the cycle) -CC: 50 mg/day for 5 days (5th-9th day of the cycle) |
did not mention timed intercourse or IUI | Human chorionic gonadotropin (hCG) at a dose of 5000-10000IU was used to trigger ovulation when a dominant follicle appeared (the average diameter ≥18 mm). | LE: 90 CC:90 |
LE: 90 CC: 90 |
Pregnancy rate ovulation rate live birth rate miscarriage rate multiple pregnancy rate |
| Pakistan | -LE: 2,5mg/day for 5 days (2nd-6th day of the cycle). The dose would be increased up to 7.55mg/day in the next cycle in non-responders -CC: 50mg/day for 5 days (2nd-6th day of the cycle). The dose would be increased up to 150mg/day in the next cycle in non-responders | Timed sexual intercourse | When at least one ovarian follicle achieved a diameter of 18-25 mm, then injection HCG 10,000 IU IM was given. |
LE: 110 CC:110 |
LE: 550 CC: 550 |
Pregnancy rate ovulation rate |
|