Table 2.
Studies including data on live birth rate per cycle following OI/IUI in women ≥ 40
| Authors | Year | Country | Study type | Patients/cycles | # of cycles | Age range | Intervention | Sperm source | Results | Notes |
|---|---|---|---|---|---|---|---|---|---|---|
| Bou Nemer et al | 2017 | United States | Retrospective | 239 cycles in women ≥ 40. Causes of infertility included unexplained (50.6%), diminished ovarian reserve (25.9%), male factor (5.4%), ovulatory dysfunction (2%), uterine factor (0.4%), and other (13%) | Not specified | Not specified | CC + GN/USF/hCG/IUI | Not specified | LBR/cycle 1.28% | LBR/cycle was 9.2% for IVF |
| Brzechffa et al | 1997 | United States | Retrospective | 363 cycles in 184 women who had failed at least 3 ovulatory cycles of CC/IUI. 111 cycles in women ≥ 40. Causes of infertility included ovulatory dysfunction, endometriosis, tubal factor, uterine or cervical factor, unexplained, or male factor | Not specified | 25–46 | GN/USF/hCG/IUI | Partner | LBR/cycle 2.7% | No pregnancies occurred with > 1500 IU of hMG was used |
| Buyalos et al | 1997 | United States | Prospective | 380 cycles in 119 women. 227 cycles in 70 women ≥ 40. Causes of infertility included ovulatory dysfunction, endometriosis, tubal or uterine factors, cervical factor, and unexplained. Couples with male factor were excluded unless using donor sperm | Not specified | 38–47 | CC (40 cycles) or CC + GN (171 cycles), or GN/USF/hCG/IUI (106 cycles), or natural cycle/OPK/donor sperm IUI (6 cycles) | Partner or donor |
For age 40 (84 cycles, 21pts), LBR/cycle 5.9% For age 41 (62 cycles, 18 pts), LBR/cycle 4.8% For age 42 (50 cycles, 17 pts), LBR/cycle 8% |
No pregnancies occurred in women ≥ 43 |
| Corsan et al | 1996 | United States | Retrospective | 469 cycles in 168 women ≥ 40 with infertility for > 1 year in setting of tubal patency and normal uterine cavity. Infertility diagnoses included unexplained (n = 35), endometriosis (n = 59), male factor (n = 63), cervical factor (n = 8), ovulatory dysfunction (n = 33). Eighteen percent of patients had multifactorial infertility | Not specified | 40–47 | CC + GN/USF/hCG/IUI (45.8%), or GN/USF/hCG/IUI (54.2%) | Not specified |
For age 40 (135 cycles), LBR/cycle 9.6% For age 41 (114 cycles), LBR/cycle 5.2% For age 42 (84 cycles), LBR/cycle 2.4% For age ≥ 43 (136 cycles), there were no live births |
|
| De Brucker et al | 2013 | Belgium | Retrospective | 764 cycles in 150 women ≥ 40, 46 primary ICSI cycles in 23 women > 40, and 129 ICSI cycles in 63 women after failed IUI (3 groups, switching after 1–3 cycles IUI, 4–6 cycles IUI, or 7–12 cycles IUI) | 1 to > 12 | 40–45 | Natural cycle/USF/hCG/IUI, CC/USF/hCG/IUI, or GN/USF/hCG/IUI | Donor | LBR/cycle 7% |
For primary ICSI, LBR/cycle 22% Time to pregnancy with IUI was 194 days versus 44 days for ICSI |
| Linara-Demakakou et al | 2020 | United Kingdom | Retrospective | 8922 cycles in 3333 women, 1604 cycles in women age 40–42, 675 cycles in women ≥ 43. Patients had a normal fertility work-up, including ovarian reserve markers and pelvic ultrasound. Tubal patency was confirmed | Not specified | Not specified | Natural cycle/OPK/IUI (48% in women 40–42, 44% in women ≥ 43), or CC vs GN/USF/hCG/IUI (52% in women 40–42, 56% in women ≥ 43) | Donor |
For age 40–42, LBR/cycle 5.4% For women ≥ 43, LBR/cycle 0.4% |
Plateau after 6 cycles in all groups. Stimulated cycles were significantly more successful in those 40–42 y. No difference for women ≥ 43 with stimulation or no stimulation. The oldest patient achieving live birth was 44 |
| Ferrera et al | 2002 | United Kingdom | Retrospective | 1056 cycles in 261 patients, 339 cycles in 61 patients > 40. 212 single women, 49 women with same-sex partnerships. Tubal patency was confirmed. Patients (n = 10) with ovulatory dysfunction were treated with CC or GN | 1 to 8 | Not specified | Natural cycle/OPK/IUI (122 cycles), CC/USF/hCG/IUI (101 cycles), or GN/USF/hCG/IUI (116 cycles) | Donor | LBR/cycle 3% | No differences in outcome by cycle protocol |
| Frederick et al | 1994 | United States | Retrospective | 210 completed cycles in 77 women ≥ 40. IUI was chosen as therapy when post-coital tests were poor (6%), semen analyses were abnormal (18%), the patient was oligo-ovulatory (22%), or no obvious diagnosis was made (54%). Tubal patency was documented in the 6 months prior to treatment | Not specified | 40–46 | CC/USF/OPK vs hCG/IUI (31%), or CC + GN/USF/OPK vs hCG/IUI (39%), or GN/USF/OPK vs hCG/IUI | Partner | LBR/cycle 1.4% | No difference in outcomes based on stimulation protocol |
| Haebe et al | 2002 | Canada | Retrospective | 1117 cycles, 106 in women ≥ 40. 24 cycles were performed in women ≥ 43. Couples had patent tubes and absence of severe male factor | Not specified | up to 47 | Natural cycle, CC, CC + GN, GN, or GnRH-agonist + GN/USF/ + / − hCG/IUI | Partner |
For all ≥ 40, LBR/cycle 8.5% For age 40–42, LBR/cycle 9.8% For age ≥ 43, LBR/cycle 4.2% For natural cycle, LBR/cycle 4.8% For CC, LBR/cycle 8% For CC + GN, LBR/cycle 0% For GN, LBR/cycle 10% For GNRHa/GN, LBR/cycle 12.5% |
There were no statistically significant differences in outcomes by cycle type. Oldest woman to have a live birth was 44 y. No difference in terms of outcomes by FSH level > 10 or < 10 |
| Harris et al | 2012 | United States | Retrospective | 262 cycles from 130 women ≥ 38 including 73 women age ≥ 40 who had been trying to conceive for > 1 year. The minimum evaluation included a semen analysis, ovulation assessment, tubal patency, and uterine cavity assessment. Infertility diagnoses included male factor (n = 21), ovulatory dysfunction (n = 8), endometriosis (n = 18), tubal factor (n = 6); diminished ovarian reserve (n = 55), uterine abnormalities (n = 10), and unexplained infertility (n = 30) | 1 to 3 | Not specified | GN/USF/hCG/IUI | Partner | LBR/cycle 2.0% | All live births occurred in the 1st cycle |
| Kang et al | 1996 | United States | Retrospective | 408 cycles from 79 women, 89 cycles in women ≥ 40. Women with abnormal HSG, endometriosis, intrauterine synchiae, or myomas were excluded. Indications for treatment were single women (n = 16) or severe male factor (n = 45) | 1 to 12 | Not specified | Natural cycle/OPK/IUI, CC/USF/OPK vs hCG/IUI, CC + GN/USF/OPK vs hCG/IUI, or GN/USF/OPK vs hCG/IUI | Donor | LBR/cycle 4.5% | No pregnancies beyond cycle #7. No pregnancies in women ≥ 45. No differences in outcome based on stimulation protocol when stratified by age including OPK vs hCG |
| Nuojua-Huttunen et al | 1999 | Finland | Retrospective | 811 cycles, 98 from women ≥ 40. Infertility for > 1 year. Women with PCOS and/or only unilateral tubal patency were excluded | Not specified | Not specified | CC + GN/USF/hCG/IUI | Partner | LBR/cycle 3.1% | No pregnancies in women > 42 |
| Osaikhuwuomwan et al | 2018 | Nigeria | Retrospective | 217 couples, 26 with female partner ≥ 40. Patients had > 1 year of infertility and bilateral tubal patency. Treatment was offered to couples with mild male factor, ovulatory dysfunction, or unexplained infertility | 1 cycle only | Not specified | CC + GN/USF/hCG/IUI | Partner | LBR/cycle 0% | |
| Soares et al | 2019 | Spain | Retrospective | 7228 cycles from 3807 patients, 868 cycles in women ≥ 40. Comparing outcomes to single women (n = 652), same-sex female couples (n = 50), and heterosexual couples using donor sperm (n = 75) to heterosexual couples using partner sperm (n = 91) of equal quality. Included ovulatory and anovulatory women. Included only women who had their first treatment during the study period | Not specified | Not specified | GN/USF/hCG/IUI | Partner and donor | In all groups LBR < 7% | No differences in outcome based on group |
| Wiser et al | 2012 | Canada | Retrospective | 247 women ≥ 40, 85 undergoing IUI results compared to women undergoing IVF (n = 124) and IVM (n = 38) from the same age group. Inclusion criteria were diminished ovarian reserve or unexplained infertility | 1 cycle only | Not specified | CC/USF/hCG/IUI (n = 46) or GN/USF/hCG/IUI (n = 39) | Not specified | For GN/IUI, LBR 2.6%. No pregnancies in CC group | No statistically significant differences in outcomes between treatment groups. Compared to women undergoing IVF over 40, LBR was 13.7% |