It is estimated that in USA about 843,820 new cases of cancer all
site would be diagnosed in women in the year 2016 out of which 89,140 will be
younger than 45 years of age.
As a result of improved knowledge and increased health
awareness combined with increased availability of screening tests and healthcare
resources many cancers are now diagnosed at a younger age than before.
According to WHO the 5 most common sites of cancer in women
are breast, colorectal, lung, cervix, and stomach cancer.
The treatment for cancers diagnosed at early stage is more
specific, less destructive and results in more Disease-free survival (DFS) and
progression-free survival (PFS) resulting in improved quality of life.
When the rapidly dividing cancer cells are targeted with
chemotherapy/ radiotherapy, the germ cells in gonads are also affected and are
destroyed.
As a result older women with decreased ovarian reserve may
end up in ovarian failure, losing the capacity to reproduce while younger women
become hypoestrogenic.
According to the International guidelines on fertility
preservation it is recommended that the physicians address the issue of
fertility preservation with all patients of reproductive age as early as possible
before initiating the treatment and keeping them informed about all the
options.
As recommended by the American Society of Clinical Oncology
and the European Society for Medical Oncology, sperm cryopreservation and
embryo/oocyte cryopreservation are standard strategies for fertility
preservations in male and female patients, respectively.
Other strategies (e.g. pharmacological protection of the
gonads and gonadal tissue cryopreservation) are still at experimental stage due
to lack of large data and guidelines..
This Systematic Review and Meta-analysis by Elgindy E et al
published in the December issue of Journal of Obstetrics and Gynecology aims to
estimate whether gonadotropin-releasing hormone (GnRH) analog administration
during chemotherapy can protect against development of ovarian toxicity.
Many studies have earlier evaluated the use of GnRH to
preserve the endocrinological and biological function of the gonads in cancer
chemotherapy/Radiotherapy with conflicting results.
Meta-analysis by Shen YW
et al published in Journal of Oncotargets and Therapy (2015 Nov 13;8:3349-59)
did show that GnRH agonists cotreatment
with chemotherapy in premenopausal women with breast cancer plays a beneficial
role in resumption of ovarian function, with a higher rate of resumption of
menses. However, treatment with GnRH agonists does not appear to exhibit its
protective effects in fertility.
Another Meta-analysis Wang C et al in PloS One(2013 Jun 21;8(6):e66360. Print 2013) also concluded a
potential benefit of GnRH cotreatment with chemotherapy in premenopausal women,
producing higher rates of spontaneous resumption of menses.
Both the trials reported an increased pregnancy rate,
however both these meta-analysis included trials with patients having breast
cancer only.
A total of 10 RCTs with 907 women were included in the
analysis comparing resumption of ovarian function between use of GnRH analogs
plus chemotherapy with chemotherapy without GnRH the analogs.
The primary outcomes were resumed ovarian function at the
longest follow-up after the end of chemotherapy. Secondary outcomes were
evaluating ovarian reserve parameters and pregnancy.
Resumption of menstrual cycles was observed in 320 of 468 in
in GnRH analog arm and 263 of 439 in the chemotherapy alone arm, which did not
reach statistical significance.
No significant difference was observed when the data was
analyzed according to different type of cancer, age below 40 vs above 40 years.
Other parameters of
ovarian capacity (baseline follicle-stimulating hormone level,
anti-Müllerian hormone level, or antral follicle count) and pregnancy rates
upon completion of chemotherapy also did not show a significantly difference
between the two arms.
On the basis of this meta-analysis, it was seen that GnRHa
co-treatment had no significant impact on rates of resumption of ovarian
function among reproductive-age women undergoing chemotherapy.
National Comprehensive Cancer Network (NCCN) guidelines have
been updated to acknowledge the use of LHRHa in preventing chemotherapy-induced
ovarian failure of hormone receptor negative breast cancer patients.
However, ovarian suppression with GnRH during chemotherapy
is still considered an experimental strategy to preserve fertility by some
international guidelines due to both the uncertainty regarding the efficacy of
this strategy and the absence of data on pregnancies and long-term ovarian
function.
References:
http://www.ncbi.nlm.nih.gov/pubmed/26241272
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