Table 4.
Studies including data on clinical pregnancy 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Agarwal et al | 1996 | United States | Retrospective | 664 cycles, 130 cycles in women ≥ 41 attempting to conceive for at least 6 months. All patients had at least one patent tube. Both ovulatory (n = 200) and anovulatory (n = 90) patients were included. Patients with severe male factor were excluded | 1 to 6 | 22–48 years | CC/USF/IUI + / − hCG trigger | Partner or donor | 5.4% CPR per cycle | No significant difference in outcomes between ovulatory and anovulatory women in any age group |
| Andersen et al | 2006 | Multiple European countries | Retrospective | 78,505 cycles using partner sperm with 2,759 cycles from women ≥ 40. 14,779 cycles using donor sperm with 1,335 cycles from women ≥ 40 | Not specified | Not specified | Not specified | Partner or donor |
6.9% CPR/cycle (partner sperm) 6.7% CPR/cycle (donor sperm) |
|
| Ashrafi et al | 2013 | Iran | Retrospective | 1348 cycles from 632 women, 248 cycles in women ≥ 40. Of women > 40, 47.6% unexplained, 23.8% ovulatory dysfunction, 9.5% male factor, 9.5% tuboperitoneal factor, 9.5% multifactorial | 1 to 6 | Not specified | CC or CC/GN or GN + USF/hCG/IUI | Partner | 8.47% CPR/cycle | |
| Auyeung et al | 2001 | United States | Retrospective | 401 cycles in 152 women ≥ 40 (58 IVF or GIFT cycles in 45 women and 343 IUI cycles in 119 women). Excluded those with tubal disease, uterine cavity anomalies, unilateral ovary or tube, advanced endometriosis, and uncorrected male factor. Infertility diagnoses were ovulatory dysfunction (48%), male factor (36.1%), endometriosis (7.6%), cervical factor (6.7%), unexplained (4.2%), and other (5%) | 1 to 8 | 40–48 years | Natural cycle/OPK/IUI (n = 38), CC/OPK/IUI with USF/hCG only if no + OPK (n = 194), or GN/USF//hCG/IUI (n = 111) | Not specified | 5.5% CPR per cycle | No difference in outcome by IUI protocol |
| Bedaiwy et al | 2009 | Canada | Retrospective | 258 cycles in 142 women ≥ 40. Infertility diagnoses were ovarian factor (46.9%), male factor (25.2%), unexplained (22.9%), endometriosis (2.7%), other (2.3%) | Not specified | Not specified | LTZ + GN/USF/hCG/IUI (134 cycles in 90 women) or FSH/USF/hCG/IUI (124 cycles in 69 women) | Not specified |
For LTZ + GN, 9% CPR/cycle For GN only, CPR/cycle 7.3% |
No statistically significant difference in CPR per cycle between women age 40–42 and women > 42. No difference with + / − LTZ but fewer cancelled cycles and lower doses of GN used |
| Belloc et al | 2008 | France | Retrospective | 9,793 cycles, 947 in women ≥ 42. Infertility diagnoses were 35.6% combined male and female factor (35.6%), male factor (23.4%), unexplained (20.3%), “cervical hostility” (12.8%), and multifactorial female causes (7.9%) | Not specified | Not specified | CC/USF/hCG/IUI (60%) or GN/USF/hCG//IUI (40%) | Not specified | CPR/cycle 8.9% | Miscarriage per pregnancy 46.4% |
| Bonow et al | 2019 | Brazil | Retrospective | 381 cycles from 261 patients. 46 cycles from women ≥ 40. Causes of infertility were unexplained (35.9%), ovulatory dysfunction (26.2%), and endometriosis (15.2%) | Not specified | Not specified | GN/USF/hCG/IUI (n = 328), GN + CC/USF/hCG/IUI (n = 42), CC/USF/hCG/IUI (n = 9), natural cycle (n = 2) | Partner | CPR/cycle 4.35% | |
| 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 | CPR/cycle 5.44% (3% for women age 40 and 7% for those ≥ 41) | CPR/cycle for IVF was 12% compared to 5.4% with IUI. For women age 40, CPR was 15% for IVF vs 3% for IUI. For women ≥ 41, CPR was 7% with IVF and 7% with IUI miscarriage rate was 46.2% |
| 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 | CPR/cycle 3.6% | 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, 21 pts), CPR/cycle 7.1% For age 41 (62 cycles, 18 pts), CPR/cycle 11.2% For age 42 (50 cycles, 17 pts), CPR/cycle 10% |
No pregnancies occurred in women ≥ 43 |
| Campana et al | 1996 | Switzerland | Retrospective | 1115 cycles in 332 couples, 202 cycles in 47 women ages 40–44, 36 cycles in 10 women > 44 | 1 to 9 | Not specified | Natural cycle/USF/OPK/IUI in women with ovulatory cycles, CC/USF/OPK/IUI or GN/USF/hCG/IUI in anovulatory women | Partner | For 40–44 CPR/cycle 2.5%, cumulative CPR 10.6% | No pregnancies in women > 44 |
| 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), CPR 13.3% For age 41 (114 cycles), CPR 7.9% For age 42 (84 cycles), CPR 4.8% For age ≥ 43 (136 cycles), there was a single clinical pregnancy |
|
| Dovey et al | 2008 | United States | Retrospective | 4199 cycles in 1738 patients, 166 cycles in 81 patients ages 41–42 and 120 cycles from 55 patients age > 42. Patients had a structurally normal uterine cavity with at least one open tube without radiographic evidence of peritubal adhesions, were ovulatory or oligo ovulatory, and had at least 5 million total motile sperm postprocessing | 1 to 6 for 41–42. 1 to 8 for > 42 | 20–48 | CC/OPK/IUI | Not specified |
For age 41–42, CPR/cycle 4.3% For women > 42, CPR/cycle 1% |
|
| 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 |
CPR/cycle 5.4% For natural cycle, CPR/cycle 3.3% For CC, CPR/cycle 0.9% For GN, CPR/cycle |
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 | CPR/cycle 5.2% | No difference in outcomes based on stimulation protocol. Miscarriage rate 72.7% |
| Gomez et al | 2014 | Germany | Retrospective | 5346 cycles in 2180 patients, 328 cycles in women 40–41 and 203 cycles in women > 41. Indication for treatment in all patients was mild male factor | Not specified | 19–45 | Natural cycle/OPK/IUI (n = 433), CC/USF/hCG/IUI (n = 596), or GN/USF/hCG/IUI (n = 4317) | Partner |
For age 40–41, CPR/cycle 8.84% For age > 41, CPR/cycle 3.43% For women 40–41, CPR/cycle for natural cycle 2.8% (n = 36) for GN 10% (n = 231), and for CC 8.2% (n = 61) For women > 41, CPR/cycle for natural cycle 4% (n = 50) for GN 4.5% (n = 111) and for CC 0% (n = 43) |
|
| 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, CPR/cycle = 17.3% For natural cycle, CPR/cycle 23.8% For CC, CPR/cycle 20% For CC + GN, CPR 10% For GN, CPR/cycle 33% For GNRHa/GN, CPR/cycle 12.5% |
There were no statistically significant differences in outcomes by cycle type. Miscarriage rate 52.6%. Oldest woman to become pregnant 46 years. 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 | CPR/cycle 4.1% | |
| Houmard et al | 2002 | United States | Retrospective | 658 cycles from 248 patients, 208 cycles from women ≥ 40. 93% of cycles included IUI. 8.7% of patients had ovulatory dysfunction | Not specified | 24–47 | CC + GN/USF/hCG/IUI | Not specified | CPR/cycle 2.4% | |
| Iberico et al | 2004 | Spain | Cross sectional | 1010 cycles from 470 patients, 49 cycles in women ≥ 40. Criteria for inclusion were > 1 year of infertility, normal ovulation history or ovulate response to medication, bilateral patent fallopian tubes, and male partner with at least two semen analyses and at least one trial sperm washing with a quantity of > 5 million motile sperm | Not specified | 18–43 | GN/USF/hCG/IUI | Partner | CPR/cycle 12.2% | |
| 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 | CPR/cycle 5.6% | No pregnancies in women ≥ 45. No differences in outcome based on stimulation protocol when stratified by age including OPK vs hCG |
| Khalil et al | 2001 | Denmark | Retrospective | 2473 cycles from 893 patients, 39 cycles in women ≥ 40. Criteria included infertility for > 2 years, at least one patent tube, and at least 1 million motile sperm on semen analysis × 2. Ovulatory and anovulatory patients were included | 1 to 9 | Not specified | CC/USF/hCG/IUI or CC + GN/USF/hCG/IUI or GN/USF/hCG/IUI | Partner | CPR/cycle 10.3% | |
| Michau et al | 2019 | France | Retrospective | 4146 cycles from 1312 couples. Patient had at least one patent fallopian tube | Not specified | 18–42 | GN/USF/hCG/IUI | Partner | CPR/cycle 8.3% | |
| 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 | CPR/cycle 4.1% | 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 | CPR/cycle 7.7% | |
| Plosker et al | 1994 | Canada | Retrospective | 381 cycles from 215 couples, 25 cycles from women ≥ 40. All patients had > 1 year infertility. Categorized as having non-severe male factor (i.e., > 1 mil sperm/mL), endometriosis, non-endometriosis tubal factor (at least one patent tube), idiopathic, ovarian dysfunction, or multifactorial infertility | 1 to 6 | Not specified | natural cycle CC, CC + GN, or GN, or GN + GNRHa/USF/OPK vs lupron or HCG trigger/IUI | Partner | CPR/cycle 4% | |
| Sahakyan et al | 1999 | United States | Retrospective | 613 cycles from 274 patients, 47 patients ≥ 40. All couples had > 1 year of infertility. Infertility diagnoses included mild male factor (n = 32), anovulation (n = 73), endometriosis (n = 55), tubal factor (n = 17), and unexplained (n = 97) | 1 to 6 | 24–47 | GN/USF/hCG/IUI | Partner | CPR/cycle 7% | |
| Schorsch et al | 2013 | Germany | Retrospective | 4246 cycles from 1612 couples, 315 cycles from 133 women ≥ 40. Included ovulatory and anovulatory patients. All patients with mild male factor. All patients with demonstrated tubal patency | 1 to 14 | 19–45 | GN/USF/hCG/IUI | Partner |
For age 40–41 (222 cycles, 94 pts), CPR/cycle 9.01% For age 42–43 (27 women, 64 cycles), CPR/cycle 6.25% For women > 43 (12 women, 29 cycles), CPR/cycle 3.45% |
Few pregnancies after the third cycle |
| Steiner et al | 2021 | Canada | Retrospective | 1596 stimulated IUI cycles, 846 from women ≥ 40. All patients had at least one patent fallopian tube. Patients with stage 3 or greater endometriosis or submucosal fibroids were excluded | 1 to 3 | 38–43 | CC or LTZ/USF/hCG/IUI (n = 161) or GN/USF/hCG/IUI (n = 685) | Partner and donor (approximately 8–10% in each group) | CPR/cycle for CC or LTZ 6.8% CPR/cycle for GN 4.8% | Women in the GN group were significantly older than the PO medication group, had lower basal FSH levels, had more follicles with stimulation, and thicker endometrial stripes but no differences in clinical pregnancy rates between PO meds and GN when controlling for these factors |
| Stone et al | 1999 | United States | Retrospective | 9963 cycles (2,825 patients ≥ 40) | Not specified | Up to 50 | No stim (n = 1367), CC (n = 149), GN (n = 128) + / − CC (n = 37), or GNRHa (n = 6)/OPK vs USF/hCG/IUI | Partner and donor |
For age 40–45, total CPR/cycle 4.7% For age > 45, CPR/cycle 0.5% |
Age 40 — 6% ongoing pregnancy/pt Age 41 — 4.7% ongoing pregnancy/pt Age 42 — 3.3% ongoing pregnancy/pt Age 43 — 2.2% ongoing pregnancy/pt Age 44 — 3.3% ongoing pregnancy/pt Age 45 — 1.2% ongoing pregnancy/pt. No other ongoing pregnancies except a single pregnancy in a 48yo pt, and two miscarriages, one in a 46yo, and one in a 47yo |
| Tay et al | 2007 | Malaysia | Retrospective | 507 cycles from 317 patients, 33 cycles in women > 40. All couples had > 1 year of infertility. Tubal patency investigated either up front or after 1–2 failed cycles of IUI. Couples were grouped by primary and secondary infertility and by diagnosis; mild male factor (n = 69), anovulation (n = 100), severe endometriosis (n = 48), tubal factor (n = 92), and unexplained (n = 198) | Not specified | Not specified | CC + GN/USF/hCG/IUI | Partner | CPR/cycle 6.1% | |
| Van der Westerlaken et al | 1998 | Netherlands | Retrospective | 1763 cycles from 466 couples, 21 women were ≥ 40. Categories included one-sided tubal pathology, mild male factor, ovulatory dysfunction, or unexplained infertility | 1 to 8 | Not specified | CC/USF/OPK vs hCG/IUI | Partner | No pregnancies occurred in women ≥ 40 | |
| 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, CPR/cycle 2.6%. No pregnancies in CC group | No statistically significant differences in outcomes between treatment groups. Compared to women undergoing IVF over 40, CPR was 16.9% |