Table 3.
Studies including data on cumulative clinical pregnancy rate 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 | 24% cumulative CPR (4 cycles) | No significant difference in outcomes between ovulatory and anovulatory women. The majority of pregnancies occurred in the first 4 cycles regardless of age (> 85%) |
| 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, 13.3% cumulative CPR For GN only, 13.0% cumulative CPR |
No difference with + / − LTZ but fewer cancelled cycles and lower doses of GN 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), cumulative CPR 23.8% For age 41 (62 cycles, 18 pts), cumulative CPR 38.9% For age 42 (50 cycles, 17 pts), cumulative CPR 29.4% |
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, cumulative CPR 10.6% | No pregnancies in women > 44 |
| Dickey et al | 2002 | United States | Prospective, observational | 3381 IUI cycles, 53 cycles in women ≥ 43. Patients were categorized as having ovulatory dysfunction, tubal factor, endometriosis, or other (cervical factor, male factor, or unexplained infertility) | 1 to 14 | Not specified | CC/OPK/IUI or CC/USF/hCG/IUI | Donor or partner | Cumulative CPR 9% (3 cycles) | No pregnancies beyond 3rd cycle |
| 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, cumulative CPR 7.4% For women > 42, cumulative CPR 1.8% |
For age 41–42, 66.7% of pregnancies occurred in first 3 cycles, 83.3% of pregnancies occurred in first 4. For > 42, one pregnancy occurred in the 3rd cycle |
| 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 | Cumulative CPR 32% | 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 | Cumulative CPR 14.3% | No difference in outcomes based on stimulation protocol. Miscarriage rate 72.7% |
| 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 | Cumulative CPR 12.3% | |
| Hull et al | 1992 | United Kingdom | Retrospective | 186 cycles, 28 cycles from women ≥ 40. Main indications were tubal damage, unexplained infertility, endometriosis, and male factor. Women with ovarian failure or serious abnormality of the uterus were excluded | Not specified | 22–46 | CC + GN/USF/hCG/IUI | Partner | For women ≥ 40, there was 1 pregnancy (4%) | |
| 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 | Cumulative CPR 42% (7 cycles) | 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 |
| Merviel et al | 2010 | France | Retrospective | 1038 cycles in 353 couples, 16 couples with female partner ≥ 40. Inclusion criteria were at least one patent fallopian tube, an FSH level below 12 IU/L, and more than 500,000 motile, normal spermatozoa | 1 to 9 | Not specified | GN/USF/hCG/IUI | Partner |
Cumulative CPR 25% Cumulative ongoing pregnancy rate (> 12 w GA) 12.5% |
|
| 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 | Cumulative CPR 39% (6 cycles) | |
| 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), cumulative CPR 21.28% For age 42–43 (27 women, 64 cycles), cumulative CPR 14.8% For women > 43 (12 women, 29 cycles), cumulative CPR 8.33% |
Few pregnancies after the third cycle |
| Vichinsartvichai et al | 2015 | Thailand | Retrospective | 466 cycles from 221 couples, 31 women > 40. Patients were excluded with tubal factor or severe male factor infertility | 1 to 4 | 21–49 | CC/USF/hCG/IUI, CC + GN/USF/hCG/IUI, or GN/USF/hCG/IUI | Partner | Cumulative CPR 3.6% | Plateau after 4 cycles |