TABLE 1.
Characteristics of the studies included
| Author | Year, country (region) | Study | Number of cycles (immediate + delayed transfers) | Age (y) | OPU cycle management | Endometrial preparation/ luteal phase support | Day of embryo development | Inclusion criteria | Exclusion criteria |
|---|---|---|---|---|---|---|---|---|---|
| He et al | 2020 (2014‐2017), China (Guangzhou) | RC | 3110 GnRH agonist protocol (1585 + 1525) | IT:31.74 ± 4.33 DT: 31.98 ± 4.23 |
Long GnRH agonist protocol (triptorelin [Diphereline]) Recombinant FSH (Gonal‐F or Puregon) Urinary HCG (uHCG) or recombinant HCG (Ovitrelle) |
(a) Natural cycle (b) Daily oral estradiol valerate tablets and 40 mg/d of intramuscular progesterone |
D3 or D5 |
Age: 20‐40 y Normal menstrual cycle. Basal FSH < 12 mIU/mL First FET cycle after whole embryo freezing using vitrification method Analog protocol with GnRh agonists or antagonists |
Donated oocytes PGD cycles Polycystic ovarian syndrome or ovulatory disorders Uterine anomalies Hydrosalpinx Uncontrolled endocrine or immune disorders or other systemic diseases |
|
1294 GnRH antagonist protocol (778 + 516) |
IT:31.37 ± 4.03 DT: 31.53 ± 4.23 |
GnRH antagonist protocol (cetrorelix [Cetrotide]) Recombinant FSH (Gonal‐F or Puregon) Urinary HCG (uHCG) or recombinant HCG (Ovitrelle) |
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| Higgings et al | 2018 (2000‐2014), Australia (Victoria) | RC |
4994 (635 + 4359) |
IT: 36.0 (26.5‐45.9) DT: 35.5(26.2‐43.9) (P = .001) |
Three GnRH analog protocols were used: (a) Short GnRH agonist (Synarel) protocol (b) GnRH agonist starting in the midluteal phase of the previous cycle (c) GnRH antagonist (Cetrotide, Orgalutran) on day 5 or when the leading follicle was ≥ 14 mm In all cases, ovarian stimulation was performed with rec FSH (400‐600 UI/d) (Gonal, Puregon). In all cases, the beginning of the cycle could be spontaneous or after the intake of contraceptive pills (30 μg ethinyl estradiol and 150 μg levonorgestrel) Triggering with HCG (Ovidrel or Pregnyl) |
(a) Natural cycle (b) Estradiol valerate 6 mg/ day and vaginal progesterone pessaries (400‐800 mg/d) or 8% progesterone gel |
NR | FET cycles with a prior fresh cycle (“fresh cycle‐ FET” interval = 25‐35 d or 50‐70 d) |
Cases from before 2000 or after 2014 FET preceded by another FET Cycles with other gaps |
| Horowitz et al |
2019 (January 2009‐December 2016), Israel (Tel Aviv) |
RC | 198 (118 + 80) | IT: 32.8 ± 5.0 DT: 34.1 ± 5.6 |
GnRH antagonist or agonist protocols. Triggering with rec HCG |
Modified natural cycle Ovulation triggering with hCG Vaginal progesterone: 400 mg Utrogestan/24 h or 200 mg Endometrin (Ferring) or a single daily application of Crinone (Merck) |
Embryos/blastocysts |
Age: 18‐45 y Regular ovulatory cycles First FET cycles after failed fresh embryo transfer |
Cycles involving donors PGD cycles Freeze‐all protocols. |
| Huang et al |
2019 (01/2013‐12/2016), China (Shanghai) |
RC | 2998 (280 + 2718) |
IT: 30.6 ± 4.3 DT: 30.9 ± 4.2 |
(a) GnRH agonist short protocol: 0.1 triptorelin (Decapeptyl; Ferring) Ovarian stimulation with 150‐225 hMG ( hMG; Anhui Fengyuan) Triggering with 5000‐10 000 IU of urinary hCG ( hCG; Lizhu Pharmaceutical Trading) (b) Progestin‐primed ovarian stimulation (10 mg medroxyprogesterone acetate (Shanghai Xinyi Pharmaceutical) Ovarian stimulation with hMG (150‐225 hMG . Triggering with (a) single use of 5000‐1000 IU of urinary hCG, (b) single dose of triptorelin (0.1‐0.2 mg) or (c) dual trigger with 1,000 IU of urinary hCG and 0.1 mg of triptorelin. |
(a) Modified natural cycles were recommended ( in case of regular menstrual cycles) Ovulation was triggered with 5,000 IU of urinary hCG. Luteal phase was supplemented with 40 mg/d of dydrogesterone (Duphaston; Abbott) (b) In irregular cycles 8 mg/d of oral micronized estradiol (Fematon, Abbott) Luteal phase was supplemented with 40 mg/d of oral dydrogesterone and 400 mg/d of vaginal progesterone (Utrogestan) |
Day 3‐4 cleavage stage embryos or day 5‐6 blastocysts |
Infertile women who underwent their first FET after the first IVF/ICSI cycle using the freeze‐all policy Day 3 or day 5 transfer |
Abnormal parental karyotyping Unilateral oophorectomy Recurrent miscarriage Uterine anomalies (congenital or acquired) Donor sperm or testicular/epididymal sperm. Moderate or severe ovarian OHSS during ovarian stimulation cycle Embryo cryopreservation > 120 d Core information missing in medical records Donated oocytes In vitro maturation oocytes PGD |
| Kaye et al | 2018 (2013‐2016), USA | RC | 344 (80 + 264) |
IT: 33.6 ± 3.8 DT: 33.52 ± 3.7 |
GnRH antagonist or agonist (leuprolide) + rFSH and/or, hMG (Gonal‐F, Follistim, Menopur) + hCG (Pregnyl or Novarel) or GnRH agonist or both |
Natural cycle and vaginal progesterone (Crinone; Merck; or Endometrin; Ferring) or GnRH agonist downregulation + oral and/or transdermal estradiol + intramuscular progesterone |
Blastocyst |
Age: 18‐40 y (a) FET after a previous ovarian stimulation cycle with one failed fresh ET (b) Freeze‐all protocol (PGD, ovarian hyperresponse/ OHSS risk, progesterone rise, planned surgery, pregnancy contraindication, lack of suitable D5 with blastocyst cryopreservation on day 6, patient preference) |
Patients without a stimulation cycle before FET (donated oocytes). Patients in whom embryo freezing was performed 120 or more days before the FET Endometrial biopsy or endometrial scratching in the cycle prior to ET |
| Lattes et al |
2017 (1/2012‐12/2014), Spain (Barcelona) |
RC |
512 (263 + 249) |
IT: 34.7 ± 4.13 DT: 35.3 ± 3.98 (P = .067) | GnRH antagonist or GnR agonist protocol, exogenous gonadotropins and GnRH agonist (triptorelin) or rhCG (Ovitrelle) |
Estradiol valerate (6 mg) or transdermal estradiol hemihydrate (150 mg/d) Vaginal micronized progesterone (600 mg/d) |
Day 3/4 embryos | Freeze‐all cycles |
BMI > 30 kg/m2 Endocrine pathologies Uterine abnormalities Chronic, autoimmune, or metabolic diseases Testicular sperm extraction Meiotic chromosomal abnormalities in testicular biopsy or altered sperm FISH Participation within the previous 6 mo, in a clinical trial with medication |
| Mass et al |
2008 (2003‐2007), USA (San Francisco) |
RC |
271 (105 + 166) |
IT: 36.3 ± 5.5 DT: 36.6 ± 5.6 |
NR | NR | Day 5‐6 blastocysts | First FET cycles after unsuccessful fresh ET | |
| Ozgur et al |
2017 (February 2015‐January 2016), Turkey (Antalya) |
RC |
1121 (756 + 365) |
IT:31.5 DT: 31.6 |
GnRH Antagonist (Cetrotide) + rFSH (Gonal‐F) + hMG (Menopur) + hCG/GnRH agonist (Gonapeptyl) or both | GnRH agonist (Lucrin Depot) or Contraceptive pill (Ginera) + oral estradiol in step‐up regime (2‐4‐8 mg) + vaginal progesterone gel (Crinone) | Blastocysts | “Freeze‐all" program |
>42 y Hysteroscopy between follicular aspiration and FET PGD |
| Santos ‐Ribeiro et al (1) |
2016 (January 2010‐November 2014), Belgium (Brussels) |
RC |
1183 (197 + 986) |
IT: 32.4 ± 4.4 DT: 32.5 ± 4.3 (P = .69) | GnRH antagonist (Cetrotide or Ganirelix) + rFSH (Gonal‐F, Puregon, Elonva) + HMG (Menopur) + HCG |
Estradiol valerate (2 mg) Vaginal micronized progesterone |
Day 4 embryos and day 5/6 blastocysts |
GnRH antagonist for downregulation hCG alone for triggering At least one FET after a previous ovarian stimulation cycle with 1 failed fresh ET |
Donated oocytes In vitro maturation PGD Triggering with GnRh agonists (alone or in combination with hCG) hCG administration for reasons other than ovulation triggering FET cycles performed with downregulation with GnRH agonist or with exogenous concomitant ovarian stimulation |
| Santos ‐Ribeiro et al (2) |
2016 (October 2010‐October 2015), Belgium (Brussels), Vietnam (Ho Chi Minh) |
RC |
333 (208 + 125) |
IT: 30.9 ± 4.1 DT: 31.8 ± 4.2 (P = .045, OR 0.97) | GnRH Antagonist (Cetrorelix o Ganirelix). rFSH (Gonal‐F, Puregon, Elonva) + HMG (Menopur )+ GnRH agonist (Triptorelin) |
Estradiol valerate (2 mg) Vaginal micronized progesterone |
D3 and day 5/6 blastocysts | First FET after a freeze‐all protocol. |
Donated oocytes In vitro maturation Blastocyst biopsy for preimplantation genetic diagnosis Previous cycle with fresh ET canceled due to thin endometrium |
| Song et al |
2019 (January 2016‐September 2018), China (Jinan) |
RC | 1540 (385 + 1155) | IT: 31.38 ± 5.19 DT: 30.99 ± 4.45 (P = .19) |
Ultra‐short, short, long and modified ultra‐long GnRH agonist protocol, GnRH antagonist protocol, mini‐stimulation protocol Recombinant FSH (Gonal, Merck or Puregon; MSD (150‐450 IU/d) and urinary hMG (hMG, Livzon) Triggering with GnRH agonist (0.2 mg triptorelin; Decapeptyl) or 250 µg rhCG (Ovitrelle; Merck) |
(a) Artificial cycle (61.7%) Estradiol valerate (2 mg/ twice daily for at least 14‐16 d, adjusting the dose afterward Injectable progesterone (20 mg/d) (b) Natural cycle (29.5% (c) Stimulation cycle (8.8%) |
D3 |
Age < 45 y Stimulation cycle completed with a freeze‐all protocol. D3 cleavage stage embryo transferred |
Patients not undergoing a stimulation cycle prior to FET Donated oocytes Embryos derived from vitrified oocytes Preceding cycles with missing data |
| Volodarsky‐ Perel et al | 2017 (1/2010‐6/2015), Israel (Jerusalem) | RC | 129 (67 + 62) | IT : 29.9 ± 4.4 DT: 29.6 ± 4.2 | GnRH Agonist (triptorelin: 3.75mg im or 0.1 mg/d sc ) + rFSH (Gonal‐F) and HMG (Menogon) and hCG |
Estradiol valerate (4‐6mg/d) Vaginal micronized progesterone (200‐300 mg/d) or intramuscular progesterone |
D 3 and D5 |
First FET cycles after fresh ET with negative β‐hCG Age 20‐38 y FET of 1‐2 vitrified embryos ≤ 3 previous ET Artificial cycle for FET |
Severe OHSS PGD |
Abbreviations: D3, day 3 cleavage embryo; D5, day 5 blastocysts, DT, delayed transfer; ET, embryo transfer; IT, immediate transfer; FET, frozen embryo transfer, FISH, fluorescence in situ hybridization; hCG, human chorionic gonadotropin; hMG, human menopausal gonadotropin; OHSS, ovarian hyperstimulation syndrome; OPU, oocyte pick‐up; PGD, preimplantation genetic diagnosis; RC, retrospective cohort; rFSH, recombinant follicle stimulating hormone.