new england journal
n engl j med
mutations in 192 Chinese patients with primary
ovarian insufficiency did not identify a mutation
We suggest that mutations in genes encoding
proteins that regulate meiosis can result in auto-
somal recessive primary ovarian insufficiency in
humans, although our findings await confirma-
tion by independent groups. However, our results
are consistent with the finding that
cient mice are infertile.
Further investigation of
in larger series of women with primary
ovarian insufficiency and in infertile men is
Jian Wang, M.S.
Boston Children’s Hospital
Boston, MA
Wenxiang Zhang, M.D.
Hong Jiang, M.D., Ph.D.
105th Hospital of People’s Liberation Army
Hefei, China
Bai-Lin Wu, M.Med., Ph.D.
Fudan University
Shanghai, China
for the Primary Ovarian Insufficiency Collaboration
Supported by grants from the Ministry of Science and Technol-
ogy of China (2010CB529601, 2013CB945404), the Science and
Technology Council of Shanghai (09JC1402400), and a Fudan
Scholar Award from Fudan University (all to Dr. Wu).
Disclosure forms provided by the authors are available with
the full text of this letter at A complete list of mem-
bers of the Primary Ovarian Insufficiency Collaboration is pro-
vided in the Supplementary Appendix.
De Vos M, Devroey P, Fauser BC. Primary ovarian insuffi-
ciency. Lancet 2010;376:911-21.
Nelson LM. Primary ovarian insufficiency. N Engl J Med 2009;
Mandon-Pépin B, Touraine P, Kuttenn F, et al. Genetic inves-
tigation of four meiotic genes in women with premature ovarian
failure. Eur J Endocrinol 2008;158:107-15.
Wang H, Sun M, Qin Y, Xia T, Ma J, Chen ZJ. Mutations in
DMC1 are not responsible for premature ovarian failure in Chi-
nese women. Reprod Biomed Online 2013;26:175-8.
Guiraldelli MF, Eyster C, Wilkerson JL, Dresser ME, Pezza
RJ. Mouse HFM1/Mer3 is required for crossover formation and
complete synapsis of homologous chromosomes during meiosis.
PLoS Genet 2013;9(3):e1003383.
DOI: 10.1056/NEJMc1310150
Cancer Risk among Children Born after Assisted Conception
To the Editor:
Williams et al. (Nov. 7 issue)
reported no increase in the overall cancer risk
among British children born after assisted con-
ception. However, the study has several limita-
tions that deserve attention because the conclu-
sions are important to both future research and
the health of children born after assisted con-
The correctness of deterministic linkages de-
pends on the completeness of the data and may
vary according to age, with lower rates of link-
age for children 1 to 9 years of age.
quently, it is possible that records were missed
or misclassified, leading to an underreporting of
the accuracy of the linkage. The authors found
overall cancer risks that were similar to those
reported in other studies, with considerable over-
lap in confidence intervals, but the studies they
refer to have indeed found a significant excess
risk. We found that the risk of early-onset acute
lymphoblastic leukemia was 2.5 times as high
among children born after assisted conception,
and the same assessment was reported in a re-
cent meta-analysis.
Our study emphasizes that
age at onset of cancer should be taken into con-
sideration and that cancers with differing causes
should not be lumped into one category.
Anastasia N. Iliadou, Ph.D.
Karolinska Institutet
Stockholm, Sweden
Eleni Petridou, M.D., Ph.D.
University of Athens
Athens, Greece
Hans-Olov Adami, M.D., Ph.D.
Karolinska Institutet
Stockholm, Sweden
No potential conflict of interest relevant to this letter was re-
Williams CL, Bunch KJ, Stiller CA, et al. Cancer risk among
children born after assisted conception. N Engl J Med 2013;369:
Li B, Quan HD, Fong A, Lu MS. Assessing record linkage
between health care and Vital Statistics databases using deter-
ministic methods. BMC Health Serv Res 2006;6:48.
Petridou ET, Sergentanis TN, Panagopoulou P, et al. In vitro
fertilization and risk of childhood leukemia in Greece and
Sweden. Pediatr Blood Cancer 2012;58:930-6.
Hargreave M, Jensen A, Toender A, Andersen KK, Kjaer SK.
Fertility treatment and childhood cancer risk: a systematic meta-
analysis. Fertil Steril 2013;100:150-61.
Adami H-O, Hunter D, Trichopoulos D, eds. Textbook of can-
cer epidemiology. 2nd ed. New York: Oxford University Press, 2008.
DOI: 10.1056/NEJMc1315232
The New England Journal of Medicine
Downloaded from at SAN FRANCISCO (UCSF) on February 12, 2016. For personal use only. No other uses without permission.
Copyright © 2014 Massachusetts Medical Society. All rights reserved.