Table 1.

Study characteristics of the selected RCTs

Study reference	Type of study	Definition of population	Normal responders definition	Intervention group (sample size)	Comparison group (sample size)
Shi et al., 2018 [23]	Multicentre, randomized, controlled trial	Women with regular menses who were undergoing their first cycle of IVF or ICSI because of tubal factors, male factors, or both. Eligible women were 20 to 35 years of age, had a normal menstrual cycle (defined as a spontaneous cycle length of ≥ 21 days and ≤ 35 days), and a duration of infertility of more than 1 year	Patients with normal ovaries at ultrasound	Freeze-all (n = 1077)	Individualization strategy based on clinical experience with fresh ET (n = 1080)
Vuong et al., 2018 [24]	Single-centre, randomized, controlled	Women without the polycystic ovary syndrome (on the basis of the Rotterdam criteria)	Patients with normal ovaries at ultrasound	Freeze-all (n = 391)	Individualization strategy based on clinical experience with fresh ET (n = 391)
Wei et al., 2019 [25]	Non-blinded, multicentre, randomized controlled trial	Women with regular menses who were undergoing the first cycle of IVF with or without ICSI with an indication of tubal, male, or unexplained infertility. Eligible women were aged 20–35 years, and had a menstrual cycle length of 21–35 days indicative of regular ovulation	Patients with normal ovaries at ultrasound	Freeze-all (n = 825)	Individualization strategy based on clinical experience with fresh ET (n = 825)
Stormlund et al., 2020 [26]	Multicentre randomized controlled trial	Women aged 18-39 years with a regular menstrual cycle (≥ 24 and ≤ 35 days) who were starting their first, second, or third treatment cycle of in vitro fertilization or intracytoplasmic sperm injection because of male, tubal, uterine, or unexplained infertility	Serum anti-müllerian hormone levels greater than 6.28 pmol/L	Freeze-all (n = 223)	Individualization strategy based on clinical experience with fresh ET (n = 230)
Popovic-Todorovic et al., 2003 [27]	Prospective randomized dual-centre study	Women at the first IVF/ICSI treatment cycle; normal basal serum FSH level (with current assays, up to 12.5 IU/l); presence of both ovaries; regular spontaneous menstrual cycle (21 ± 35 days); maximum age 39 years at the onset of treatment and no evidence of endocrine disorders	Expected normal responders	Individualized dose based on algorithm (n=131)	Standard dose (150 IU) (n=131)
Olivennes et al., 2015 [28]	Prospective, randomized, controlled, multiregional, open-label, phase IV study	Women with spontaneous menstrual cycle of 21–35 days; BMI < 30 kg/m2; basal serum FSH level 12 IU/L or less; no previous poor response to ovarian stimulation in two or more assisted reproductive technique cycles; no previous hyper-response to ovarian stimulation (defined as 25 or more oocytes retrieved) in two or more assisted reproduction technique cycles; no previous severe OHSS; no PCOS or three or more spontaneous abortions	Patients with no poor or hyper response	Individualized dose based on algorithm (n = 96)	Standard dose (150 IU) (n = 104)
Nyboe-Andersen et al., 2017 [29]	Randomized, multicentre, assessor-blinded, non-inferiority trial (ESTHER-1).	Women undergoing their first IVF/ ICSI cycle; BMI 17.5–32.0 kg/m2, regular menstrual cycles of 24–35 days, presence of both ovaries, and basal FSH serum concentration 1–15 IU/L, no endometriosis stage III–IV, no history of recurrent miscarriage and no use of hormonal preparations	Expected normal responders	Individualized dose based on algorithm (n = 665)	Standard dose (150 IU) (n = 661)
Allegra et al., 2017 [30]	Two-arm, single-centre, prospective, randomized, interventional trial	Women at the first IVF/ICSI cycle, female age between 18 and 40 years, BMI between 18 and 25 kg/m2, serum AMH concentrations between 1.0 and 4.0 ng/ml, basal serum day 3 FSH ≤ 15 IU/l, normal regular menstrual cycles, ranging from 25 to 33 days in length, normal uterine cavity, presence of both ovaries, no PCOS, no severe endometriosis, no previous ovarian surgery, absence of ovarian cysts, no use of hormonal contraception in the previous three months, absence of metabolic or endocrinological disease	Patients with normal values of AMH and basal FSH	Individualized dose based on algorithm (n = 95)	Individualization strategy based on clinical experience (150 IU ≤35 ys; 225 IU > 35 ys) (n = 99)
Bosch et al., 2019 [31]	Randomized, controlled, assessor-blind trial	Women who had participated in cycle 1 (women undergoing their first IVF/ICSI cycle, 18–40 years of age, with regular menstrual cycles, diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility) and failed to achieve an ongoing pregnancy were eligible for cycle 2 and women who failed to achieve an ongoing pregnancy in cycle 2 were eligible for cycle 3. Patients with severe OHSS in a previous cycle, or patients with any clinically relevant change to any of the eligibility criteria or any clinically relevant medical history since the previous cycle were not eligible for enrolment	Normal responders	Individualized dose based on algorithm (n = 347)	Individualization strategy based on clinical experience (n = 354)
Friis Petersen et al., 2019 [32]	Dual-centre, randomized controlled trial	Women with normal menstrual cycles of 24–35 days interval presumed to be ovulatory; bodyweight < 75 kg; FSH ≤ 12IU/L; two ovaries accessible to oocyte retrieval; uterus with presumed normal function based on sonography; no PCOS; no endometriosis grade III/IV; no hydrosalpinx on ultrasound, no recurrent miscarriages (≥3), absence of major medical disorders	Expected normal responders	Individualized dose based on algorithm (n = 149)	Standard dose (150 IU) (n = 72)
Ishihara et al., 2021 [33]	Randomized, controlled, assessor-blind, multicentre, non-inferiority trial	Japanese women between 20 and 40 years, BMI between 17.5 and 32 kg/m2, first IVF/ICSI cycle. Eligibility criteria included women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility. Additionally, women had to have regular menstrual cycles of 24–35 days, presence of both ovaries and early follicular phase FSH serum levels of 1–15 IU/l.	Expected normal responders	Individualized dose based on algorithm (n = 170)	Standard dose (150 IU) (n = 177)
Qiao et al., 2021 [34]	Randomized, controlled, multi-centre, assessor-blind, non-inferiority trial	Asian reproductive-aged women between 20 and 40 years, BMI between 17.5 and 32 kg/m2, first IVF/ICSI cycle. Eligibility criteria included women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility. Additionally, women had to have regular menstrual cycles of 24–35 days, presence of both ovaries and early follicular phase FSH serum levels of 1–15 IU/l. Women with endometriosis stage III/IV, history of recurrent miscarriage and with one or more follicles 10 mm observed prior to randomization were excluded	Expected normal responders	Individualized dose based on algorithm (n = 499)	Standard dose (150 IU) (n = 510)
Van Tilborg et al., 2017 [35]	Multicentre prospective cohort study with two embedded RCT	Infertile women younger than 44 years starting their first IVF or ICSI treatment, or the first IVF or ICSI treatment after a previous live birth were eligible for inclusion. Participants had to have a regular menstrual cycle (on average 25–35 days) and no significant uterine or ovarian abnormalities on transvaginal ultrasound. Women with polycystic ovary syndrome (PCOS), endocrine or metabolic abnormalities or women who opted for oocyte donation were not included in the trial	Expected normal responders	Individualization of the starting dose based on AFC (individualization policy based on clinical experience). (n = 747)	Standard dose (150 IU) (n = 769)