Table 2.
Characteristics of the included studies—females. Summary of cohort studies assessing the prevalence of gonadotoxicity in women.
| First Author, Year of Publication | Country | Study Design | Number of Participants of Interest (Females) | Age of Participants of Interest at Time of Diagnosis/Therapy (Years, Range) | Age (Years, Mean ± SD) at Outcome/Evaluation |
Follow-Up After Diagnosis/Treatment, Length in Years (Range) | Tumor Type Number (%) | Chemotherapy, Details | Radiotherapy, Details | Suspected Infertility |
Comments |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Al-Badawi et al., 2010 [24] | Saudi Arabia | Retrospective | 4 | 23 (18–36) | Not specified | 2.67 (0.83–5) | RC | Not specified | Yes, without specifications | 2/4 (50%) | Calculated in women with persistent amenorrhea. Laparoscopic ovarian transposition to paracolic gutters with uterine conservation. |
| Cercek et al., 2013 [25] | USA | Retrospective | 49 | 31–35 (21–50) | Not specified | >0.5 (range not specified) | CRC | FOLFOX standard modified mFOLFOX |
No | 8/49 (16%) | Calculated in women with persistent amenorrhea (>1 year). |
| Barahmeh et al., 2013 [26] | Jordan | Retrospective | 4 | Not specified | Not specified | 3.5 (2.83–4.17) | RC | 5-FU concomitantly with radiotherapy | Estimated irradiation dose to both ovaries after pelvic radiotherapy: 2.1 Gy for three patients and 18 Gy for one patient. External pelvic irradiation (45–60 Gy) |
1/4 (25%) | Calculated in women with hypergonadotropic hypogonadism. Bilateral ovarian transposition to the paracolic gutter. |
| Wan et al., 2015 [27] | China | Retrospective | 123 | CC: 36 (17–40) RC: 35 (24–40) |
Not specified | CC: 3.16 (1.52–6.32) RC: 3.35 (1.21–6.36) |
CC 58.6 RC 41.4 |
FOLFOX XELOX Capecitabine only |
CC: no RC: intensity-modulated radiotherapy to pelvis (total dose 45–55 Gy in 25–30 fractions) |
colon cancer 3/72 (4.2%) rectal cancer 48/51 (94.1%) |
Calculated in women with persistent amenorrhea > 1 year. |
| Levi et al., 2015 [28] | Israel | Prospective | 11 | 36 | 36.5 | 0.5 | CRC | FOLFOX or XELOX |
In 1 patient | 0/11 (0%) | Calculated in women with hypergonadotropic hypogonadism. |
| Sioulas et al., 2017 [29] | USA | Retrospective | 22 | 39 (26–45) | Not specified | 2.42 (0.09–6) | RC (90.9) AC (9.1) |
FOLFOX CAPOX FOLFOX/bevacizumab FOLFOX/FOLFIRINOX Capecitabine 5-FU Mitomycin C |
RC: 5000 to 5400 cGy to the rectal tumor 4500 cGy to the pelvic nodes AC: 5600 cGy to the primary tumor 4500 cGy to the pelvic nodes |
6/18 (33.3%) | Calculated in women with hypergonadotropic hypogonadism. Only 18 patients were evaluable for ovarian function. Nineteen patients underwent OT. |
| Sahin et al., 2019 [30] | Turkey | Retrospective | 60 | 40 (19–50) | Not specified | Min. 1 | CC | 5-FU alone 5-FU + oxaliplatin FOLFOX CAPOX |
No | 10/49 (20.4%) | Calculated in women with persistent amenorrhea >1 year. |
| Svanström Röjvall, 2020 [31] | Sweden | Prospective | 6 | Not specified | Not specified | 2 | RC | Yes | Short course (5 Gy × 5) Long course (2 Gy × 25 or 1· 8 Gy × 28) + 3 fractions of boost |
5/6 (83.3%) | Calculated in women with undetectable AMH. |
| Velez, 2021 [32] | Canada | Retrospective | 361 | Not specified | Not specified | Not specified | CRC | Not specified | Not specified | 32/361 (8.9%) | Calculated in women with infertility diagnosis using the health administrative database. |
| Hilal et al., 2022 [33] | USA | Retrospective | 76 | 43 (20–49) | Not specified | 4.48 (0.48–15.44) | RC | FOLFOX/XELOX 5FU/LV Xeloda Cisplatin–Etoposide |
Median dose: 50 Gy (25–56) 25 (5–28) fractions 3D-CRT IMRT |
56/76 (75%) | Twenty-six (34%) underwent OT. Calculated in women with hypergonadotropic hypogonadism. |
| Shylasree, 2022 [34] | India | Retrospective | 46 | 25.2 | Not specified | 3.5 (0.42–6.75) | RC | Capecitabine 5-FU + oxaliplatin |
Neoadjuvant chemoradiation: 50.4 Gy in 28 fractions (1.8 Gy) with concurrent capecitabine. Short-course RT: 25 Gy in five fractions (5 Gy). | 15/43 (34.9%) | Calculated in women with hypergonadotropic hypogonadism and a need for puberty induction. |
| Falk, 2022 [35] | Norway, Sweden, Finland | Prospective | 16 | 35 (range 20–40) | Not specified | 1–5 | CC RC AA CRC |
FOLFOX CAPOX Nordic FLOX |
No | 0/13 (0%) | Calculated in women with hypergonadotropic hypogonadism, amenorrhea, and undetectable AMH. |
Note: The studies are sorted by year of publication. Age and duration of follow-up are given as years with mean (SD) or with range where such data are available. Abbreviations: Diagnosis: CRC = colorectal cancer; CC= colon cancer; RC = rectal cancer; AC = anal cancer; AA = appendiceal adenocarcinoma. Chemotherapy: FOLFOX = 5-fluorouracil, leucovorin [folinic acid], and oxaliplatin; XELOX = capecitabine and oxaliplatin; CAPOX = capecitabine and oxaliplatin; Nordic FLOX = 5-FU bolus, folic acid, and oxaliplatin; 5-FU = 5-fluorouracil; LV = leucovorin. Radiotherapy: Parameters: AMH: anti-Müllerian hormone. Other: OT = ovarian transposition.