Table 1.
Characteristics of included studies
| Studies | Country | Study design | Type of treatment (subgroup of patients) | Participants | Interventions | Comparator |
|---|---|---|---|---|---|---|
| Luteal-phase stimulation | ||||||
| Buendgen 2013 | Germany | Prospective cohort |
IVF (general) |
40 participants (10 LPS and 30 eFPS) Incl crit: 18–36 years; ≤ 3 earlier unsuccessful IVF Excl crit: PCOS, EDT ≥ III and expected poor response |
LPS: uFSH 300 IU-GnRH antagonists Start: days 19–21 |
eFPS: rFSH or hMG 150–225 IU/day-GnRH antagonists |
| Lin 2018 | Taiwan | Prospective cohort |
IVF (poor ovarian reserve) |
60 participants (30 LPS and 30 eFPS) Incl crit: Bologna criteria Excl crit: previous oophorectomy, exposure to cytotoxic or pelvic irradiation for malignancy, positive screening for recurrent pregnancy loss |
LPS: hMG 225 IU/day + CC 100 mg/day - MPA 10 mg/day Start: day 15–18 |
eFPS: rFSH 300 IU/day + rLH 150 IU/day - GnRH antagonists |
| Llacer 2020 | Spain | RCT |
IVF (poor ovarian reserve) |
60 participants (27 LPS and 30 eFPS) Incl crit: Bologna criteria, < 41 years, regular menstrual cycles of 21–35 days, indication for IVF with 300 UI rFSH, presence of both ovaries Excl crit: Follicles > 10 mm in the randomization visit, EDT III/IV, concurrent uterine pathology and concurrent participation in another study |
LPS: rFSH 300 IU/day + rLH 150 IU/day - GnRH antagonists Start: 4 days after an LH positive test |
eFPS: rFSH 300 UI/day + rLH 150 UI/day - GnRH antagonists |
| Wang 2016 | China | Retrospective cohort |
IVF (general) |
2112 participants (727 LPS and 1385 eFPS) | LPS: Letrozole 2.5 mg/day (for 5 days) + hMG 225 IU/day (2–7 days after ovulation) - MPA 10 mg/day | eFPS: hMG 150 IU/day or more - Triptorelin 100 mcg/day |
| Zhang 2018 | China | Retrospective cohort |
IVF (poor ovarian reserve) |
385 participants (154 LPS and 231 eFPS) Incl crit: Bologna criteria |
LPS: CC 50–100 mg/day + hMG 75–150 IU/day (2–7 days after ovulation) - Dydrogesterone 20 mg/day | eFPS: CC 50–100 mg/day (from day 3 to 7) + hMG 75–150 IU/day (from day 8) |
| Double stimulation (DuoStim) | ||||||
|
Martazanova 2018 |
Russia | RCT |
IVF (poor ovarian reserve) |
148 participants (79 Duostim and 72 eFPS) Incl crit: < 43 years; АМH < 1.2 ng/ml; AFC < 6; FSH > 11 IU/ml Excl crit: uterine fibroids, deep EDT, cancer |
DuoStim: not specified Start: day 2 for follicular stim and 4 days after oocyte retrieval |
eFPS: not specified |
| Ubaldi 2015 | Italy | Before-after study |
IVF (poor ovarian reserve) |
34 participants (17 DuoStim and 17 eFPS) Same patient, less than 6 months between the conventional and the double stimulation. Incl crit: < 7 oocytes in previous cycle, AMH ≤ 1.6 ng/ml and antral follicle count ≤ 7 Excl crit: not specified |
DuoStim: Gonadotrophins - GnRH antagonists. Same protocol for both stimulations. After the first oocyte retrieval, GnRH antagonist daily was administrated for 3 days. Start: day 2 for follicular stim and 4 days after oocyte retrieval |
eFPS: not specified |
| Vaiarelli 2020 | Italy | Prospective cohort |
IVF (poor ovarian reserve) |
197 participants (100 DuoStim and 197 eFPS) Incl crit: Bologna criteria for poor responders Excl crit: not specified |
DuoStim: rFSH 300 IU/day + rLH 150 IU/day - GnRH antagonist. Same protocol for both stimulations. Start: day 2 for follicular stim and 5 days after oocyte retrieval |
eFPS: rFSH 300 IU/day + rLH 150 IU/day - GnRH antagonists |
| Random-start stimulation | ||||||
| Muteshi 2018 | UK | Retrospective cohort | Oocyte and embryo cryopreservation (cancer) |
137 participants (24 random-start and 103 eFPS) Incl crit: recently diagnosed with cancer and referred for fertility preservation. Excl crit: not specified |
Random-start: 3 days of cetrorelix 0.25 mg followed by Gonadotrophins on fourth day - GnRH antagonists Start: at any point after menstrual day 5 |
eFPS: rFSH or hMG 250 IU/day – GnRH antagonists |
| More than 2 intervention groups | ||||||
| Cakmak 2013 | USA | Retrospective cohort | Oocyte and embryo cryopreservation (cancer) |
128 participants (13 lFPS, 22 LPS and 93 eFPS) Incl crit: recently diagnosed with cancer and in preparation for chemotherapy/radiotherapy or bilateral oophorectomy Excl crit: history of infertility or previous gonadotoxic treatment |
Gonadotropins ± aromatase inhibitor – GnRH antagonists lFPS: start after day 7 with follicle > 13 mm. LPS: start on day 2–3 after triggering or after high progesterone detection |
eFPS: Gonadotropins ± aromatase inhibitor – GnRH antagonists |
| Cavagna 2018 | Brazil | Retrospective cohort | Oocyte cryopreservation (breast cancer) |
109 participants (42 eFPS, 20 lFPS and 47 LPS) Incl crit: breast cancer with indication of chemotherapy, ≤ 40 years Excl crit: advaced or metastatic disease, ≥ 41 years |
lFPS: hMG 150–300 IU/day + aromatase inhibitor – GnRH antagonists concomitant with gonadotropins. Start with the presence of dominant follicle > 10 mm LPS: rFSH 150–300 IU/day + aromatase inhibitor – GnRH antagonists start when evidence of follicle rupture and endometrium secretory pattern |
eFPS: hMG 150–300 IU/day + aromatase inhibitor – GnRH antagonists start with the absence of dominant follicle > 10 mm |
| Checa 2015 | Spain | RCT | Egg donors |
11 participants (6 lFPS, 5 LPS, and 11 eFPS) All participants had an eFPS cycle followed by either an lFPS or LPS cycle Incl crit: 18–32 years, BMI 12–28, baseline FSH > 10 Excl crit: history of chemotherapy, gonadotoxic drugs, infertility, ovarian surgery, PCOS male factor |
lFPS: Ganirelix 0.25 mg on day 10 until E2 < 60 pg/ml followed by rFSH 225 IU/day – GnRH antagonists LPS: Ganirelix 0.25 mg on day 20 until E2 < 60 pg/ml, followed by daily rFSH 225 IU/day – GnRH antagonists |
eFPS: rFSH 225 IU/day – GnRH antagonists |
| Jin 2018 | China | Retrospective cohort |
IVF (poor ovarian reserve) |
260 participants (132 eFPS, 76 DuoStim, 52 LPS) Incl crit: Bologna criteria Excl crit: basal FSH > 25 mIU/ml, EDT III/IV, BMI < 18 or > 30 kg/m2 |
LPS: CC 50–100 mg/day or letrozole 5 mg/day lasting 5 days + hMG 150–300 UI/day -GnRH antagonists. DuoStim: Start: day 3 for follicular stim and 1–3 days after oocyte retrieval LPS: Start: 1–3 days after natural ovulation |
eFPS: CC 50–100 mg/d or letrozole 5 mg/d (from day 3 to 7) + hMG 150–300 IU/d (from day 8) -GnRH antagonists |
| Qin 2016 | China | Retrospective cohort |
IVF (general) |
150 participants (50 lFPS, 50 LPS and 50 eFPS) Incl crit: <42 years; regular menstrual cycles the previous 3-month; AFC >3 or FSH <12 IU/L, BMI 17–27 kg/m2 Excl crit: AFC <3 or FSH >12, EDT III/IV, PCOS, receipt of hormone treatments within the previous 3-month period, including oral, any contraindications to COH |
lFPS: hMG 150–225 IU/d + CC 25 mg/d + GnRH agonist + MPA 10 mg/d. Start day 6–14 with follicle >10 mm. + E2 > 75. LPS: hMG 150–225 IU/d + CC 25 mg/d. Start after day 14 with P4 > 6.5 mg or corpora luteum |
eFPS: hMG 150–225 IU/d + MPA 10 mg/d + CC 25 mg/d |
| Von Wolf 2016 | Germany | Retrospective cohort | Oocyte cryopreservation (cancer) |
684 participants (109 LFPS 103 LPS and 472 eFPS) Incl crit: Not specified Excl crit: Not specified |
lFPS: rFSH or hMG – GnRH antagonists Start day 6–14 LPS: rFSH – GnRH antagonists. Start after day 14 |
eFPS: rFSH or hMG – GnRH antagonists |
LPS, luteal-phase stimulation. eFPS, early follicular phase stimulation. lFPS, late follicular phase stimulation. AFC, antral follicular count. Spont cycle, spontaneous cycle. Incl crit, inclusion criteria. Excl crit, exclusion criteria. IVF, in vitro fertilization. PCOS, polycystic ovarian syndrome. COH, controlled ovarian hyperstimulation. EDT, endometriosis. BMI, body mass index. E2, estradiol. rFSH, recombinant follicle-stimulating hormone. rLH, recombinant luteinizing hormone. hMG, human menopausal gonadotropin. CC, clomiphene citrate. MPA, medroxyprogesterone