Table I.
Studies associating telomere length with female infertility.
| Authors/(Refs.) | Sex | Association with infertility | Relative TL | Method | Population no. | Population age (years) | Population country | Sample type | Infertility factor | Conclusions |
|---|---|---|---|---|---|---|---|---|---|---|
| Hapangama et al, 2008 (51) | F | + | Ln | RT-PCR | -(n=29), endo -(n=27), non-endo |
18-46 25-44 |
UK | Endom Bx | Endo | • TL is longer in endometria of F with endo during the implantation window. Tissue TL and LTL are not correlated • LTL is (+) correlated with circulating estradiol |
| Butts et al, 2009 (52) | F | + | Sh | RT-PCR | -(n=12) OOI -(n=42), CNTL (IVF) |
30-37 23-37 |
US | G | DOR | • GTL shortening and diminished TA are associated with occult ovarian insufficiency |
| Hapangama et al, 2010 (35) | F | + | Ln | RT-PCR | -(n=38), endo -(n=35), non-endo |
18-45 25-38 |
UK | Endom Bx | Endo | • (+) correlation between endometrial TL and both glandular and stromal expression of nucleolin |
| Hanna et al, 2009 (63) | F | + | Ln | RT-PCR | -(n=34), POF -(n=95), SAB history -(n=108), HC -(n=46), fert |
21-50 24-45 17-55 37-54 |
CA | L | POF | • F with POF have longer LTL |
| Kuhn et al, 2010 (55) | F | + | Sh | Q-FISH | -(n=22), STIC -(n=134) HGSC |
N/A | US | Tubal epithelial cells | TFI/Ca | • Support of the proposal that STICs are precursors of HGSC potentially an early event in ovarian HGSC |
| Treff et al, 2011 (53) | F | + | Sh | RT-PCR | -(n=21) | 32-42 | US | Oocytes (polar bodies) | DOR | • Lower telomere DNA in aneuploid polar bodies compared to euploid polar bodies (-3.04-fold, P = 0.016) • Oocytes with telomere DNA deficiency are prone to aneuploidy development during meiosis |
| Kuhn et al, 2011 (64) | F | + | Ln | Q-FISH | -(n=219), ovarian Ca -(n=106), HGSC -(n=26), LGSC -(n=56), OCCC -(n=31), LGEC |
23-88 | US, TW | SC | Ca/DOR | • TL significantly differs by histologic type in ovarian Ca • OCCC has longer mean relative TL compared with the other histologic types |
| Valentijn et al, 2013 (62) | F | + | Ln | RT-PCR | -(n=60), pre-menopausal, normal -(n=15), post-menopausal -(n=20), endo |
23-49 46-78 18-49 |
UK | Endom cells | Endo | • Showed significantly higher expression of TA in F with endo • Longer mean TLs in F with endo |
| Turner and Hartshorne, 2013 (39) | M/F | + | Sh | Q-FISH | -(n=45), M -(n=32), F |
21-49 25-42 | UK | Sperm (semen), oocytes | C | • STL not crucial for M fert • TL reset in embryo after fertilization • TL shortening during human oocyte maturation • Oocyte-induced sperm telomere DNA modification, via a recombination-based TL increase towards the blastocyst stage |
| Cheng et al, 2013 (42) | F | + | Sh | RT-PCR | -(n=45), <38yo -(n=35), ≥38yo |
29.2+3.4 41.4+1.9 |
TW | Oocyte- cumulus complex | C | • Mature oocytes have longer TL than immature oocytes • Good-quality embryos have longer TL than poor-quality embryos (cut-off value of the T/S ratio on embryonic Day 3 was 4.235) |
| Dracxler et al, 2014 (91) | F | + | Ln | q-PCR | -(n=86), endo -(n=21), HC |
33 36 |
BZ | Lymphoc | Endo | • Lymphoc. TL is significantly longer in F with endo • High variety in lymphocyte telomere content in F with endo |
| Li et al, 2014 (58) | F | + | Sh | RT-PCR | -(n=698), PCOS -(n=611), HC |
26.42±0.19 28.77±0.27 |
CN | L | PCOS | • LTL is shorter in F with PCOS • LTL is not associated with biochemical traits in F with PCOS • (−) correlation between healthy CNTL LTL and serum DHEAS |
| Yu et al, 2014 (41) | F | + | Sh | RT-PCR | (n=6), no endo/PID) for laparoscopic tubal ligation | N/A | US | ET (Isolation of eMSC lines) | C | • Disrupted GJIC in endometrial SC reduced the mean TL by 45%. Disrupted GJIC causes ED, which is associated with abnormal uterine bleeding, failed embryonic implantation, infert, or endom Ca |
| Valentijn et al, 2015 (62) | F | + | Ln | RT-PCR, Q-FISH | -(n=70), fert (blood samples) -(n=74), HC (endom Bx) -(n=10), endo (ectopic and eutopic endom samples) -(n=8), HC in mid-secretory phase |
18-46 23-45 24-47 26-45 |
UK | L, ET | Endo | • Endom TL is longer than donor-matched LTL andis (−) correlated with serum progesterone levels • Short TL is observed in proliferating EECs in vivo and in vitro • Ectopic endom lesions have a higher epithelial telomeric signal than that in the uterine (eutopic) endom of the same individuals |
| Czamanski-Cohen et al, 2015 (44) | F | + | Sh | Q-PCR | -(n=20), IVF Tx -(n=10), HC |
29.3±4.3 28.6±3.4 |
IL | L | Infert | • Patients seeking IVF treatment exhibited shorter TL than healthy controls. |
| Pedroso et al, 2015 (38) | F | − | N/A | RT-PCR | -(n=150), PCOS -(n=124), HC |
29.36±5.18 | BZ | L | PCOS | • No difference in LTL between PCOS and healthy |
| Miranda- Furtado et al, 2016 (37) | F | − | N/A | RT-PCR | -(n=45), PCOS -(n=52), HC |
18-37 | BZ | L | PCOS | • No difference in telomere content between CNTL and PCOS • TL shortening after progressive resistance training intervention |
| Li et al, 2017 (59) | F | + | Sh | RT-PCR | -(n=65), PCOS (IVF) -(n=98), non-PCOS (IVF) |
30.3±4.3 31.7±3.8 |
CN | L, G | PCOS | • F with PCOS have shorter GTL • F with lower TA levels and shorter TL have an earlier onset of infert symptoms |
| Wei et al, 2017 (56) | F | + | Ln | RT-PCR | -75 F, PCOS -81 F, non-PCOS (IVF) |
28.36±2.55 28.09±2.26 |
CN | L, G | PCOS | • No difference in LTL between PCOS and non-PCOS • GTL is longer in women with PCOS |
| Wang et al, 2017 (57) | F | + | Ln | RT-PCR | -(n=40), PCOS -(n=35), HC |
24.78±3.54 26.33±2.15 |
CN | L | PCOS | • LTL is significantly longer in F with PCOS • (+) correlation between LTL and testosterone levels |
| Kalyan et al, 2017 (36) | F | - | N/A | RT-PCR | -(n=25), PCOS -(n=41), HC |
40.3±3.4 42.5±4.2 |
CA | L | PCOS | • No difference in LTL between PCOS and CNTL |
| Sofiyeva et al, 2017 (61) | F | + | Ln | (Telo TAGGG) PCR ELISA | -(n=14), IE -(n=17), FE -(n=16), HC |
30.42±1.36 40.82±1.36 47.9±0.96 |
TR | Eutopic endom cystic wall/ovarian cortex, venous blood | Endome- triosis | • High TA was found in the secretory phase of infertile endo women compared to that of healthy patients |
| Xu et al, 2017 (54) | F | + | Sh | RT-PCR | -(n=120), POI (IVF) -(n=279), HC (IVF) |
32.95±4.27 29.98±4.28 |
CN | L, G | Premature ovarian insufficiency | • Shorter LTL and GTL in women with POI • LTL decreases 0.067 T/S every year from age 21 up till 39 years • GTL decreases 0.089 T/S every year from age 23 to 39 years • Biochemical POI is associated with 0.69 T/S LTL reductions and 0.98T/S GTL reductions |
| Pollack et al, 2018 (40) | F | + | Sh | RT-PCR | -(n=1505), parous -(n=444), nulliparous |
20-44 | US | L | Combination | • Leukocyte T/S ratio 4.2% (95% CI: 0.9, 7.3) • TLparous < TLnulliparous • Parity: 116 fewer base pairs (95% CI: 26, 204) |
(+), positive; (−), negative; BR, Brazil; Bx, biopsy; C, combination; CA, Canada; CI, confidence interval; CN, China; CNTL, control; Ca, cancer; DHEAS, dehydroepiandrosterone sulfate; DK, Denmark; DOR, diminished ovarian reserve; ED, endometrial dysfunction; EEC, endometrial epithelial cells; ET, endometrial tissue; F, female; FE, fertile endometriosis; FISH, quantitative fluorescent in situ hybridization; G, granulosa cells; GJIC, gap-junctional intercellular communication; GTL, granulosa cell telomere length; HC, healthy control; HGSC, high-grade serous carcinoma; HGSC, high-grade serous carcinoma; IE, infertile endometriosis; IN, India; IT, Italy; IVF, in vitro fertilization; L, leukocytes; LGEC, low-grade endometrioid carcinoma; LGSC, low-grade serous carcinoma; LTL, leukocyte telomere length; Ln, longer; Lymphoc, lymphocytes; M, male; N/A, not applicable; OCCC, ovarian clear cell carcinoma; OOI, occult ovarian insufficiency; PCOS, polycystic ovary syndrome; PID, pelvic inflammatory disease; POI, primary ovarian insufficiency; RT-PCR, reverse transcription-polymerase chain reaction; SAB, spontaneous abortion; SC, stromal cells; STIC, serous tubal intraepithelial carcinoma; STL, sperm telomere length; Sh, shorter; T-T, telomere-telomere; TA, telomerase activity; TFI, tubal factor infertility; TL, telomere length; TR, Turkey; TW, Taiwan; Tx, treatment; UK, United Kingdom; US, United States; endo, endometriosis; endom, endometrium/al; fert, fertile/fertility; infert, infertile/infertility; yo, years old.