Human Reproduction, Vol.32, No.10 pp.

2123–2129, 2017
Advanced Access publication on September 9, 2017 doi:10.1093/humrep/dex276

ORIGINAL ARTICLE Reproductive endocrinology

Random start ovarian stimulation for

fertility preservation appears unlikely
to delay initiation of neoadjuvant
chemotherapy for breast cancer
Joseph M. Letourneau1,*, Nikita Sinha1, Kaitlyn Wald1,2, Eve Harris1,
Molly Quinn1, Tal Imbar4, Evelyn Mok-Lin1, A. Jo Chien3,
and Mitchell Rosen1
1
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, 499 Illinois Street, 6th Floor, San Francisco, CA
94158, USA 2Department of Obstetrics and Gynecology, University of Washington, Health Sciences Building, 6th Floor, BB Wing,
1959 NE Pacific St, Seattle, WA 98195, USA 3Department of Medicine, Division of Hematology and Oncology, University of California,
1600 Divisadero St., Second Floor, San Francisco, CA 94115, USA 4Department of Obstetrics & Gynecology, Hadassah-Hebrew University
Medical Center, P.O.Box 12000, Jerusalem 91120, Israel

*Correspondence address. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA,
USA. Tel: +1-415-353-7475, E-mail: joseph.letourneau@ucsf.edu

Submitted on May 24, 2017; resubmitted on July 9, 2017; accepted on August 2, 2017

STUDY QUESTION: Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast
cancer?
SUMMARY ANSWER: Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely
to delay time to initiation of neoadjuvant chemotherapy start.
WHAT IS KNOWN ALREADY: Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer
and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to
delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not
well-understood.
STUDY DESIGN, SIZE, DURATION: Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consult-
ation prior to starting neoadjuvant chemotherapy for breast cancer.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A chart-review was performed. Study inclusion criteria were female sex; age
18–45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evalu-
ation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were
obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those
who did not using T-tests and linear modeling.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy
were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent
ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to
chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ±
18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for
those who did not undergo ovarian stimulation (P < 0.001).
LIMITATIONS REASONS FOR CAUTION: Retrospective study with potential for selection bias among those who underwent ovarian
stimulation versus those who did not. Reasons for caution include the possibility of unmeasured differences among those who did and did not
undergo ovarian stimulation, including: patients’ and providers’ perceptions of the urgency to start chemotherapy, ongoing oncology work-up

Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2017. This work is written by (a) US
Government employee(s) and is in the public domain in the US.
2124 Letourneau et al.

and treatment planning, FP decision-making, and the pursuit of second and third opinions. The difference in time from referral to FP consult-
ation may have also influenced patients’ decisions about whether to undergo ovarian stimulation.
WIDER IMPLICATIONS OF THE FINDINGS: In this study, FP with random start ovarian stimulation was not associated with a delay
cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Patients undergoing neoadjuvant chemotherapy
should be informed of these findings to avoid unnecessary anxiety due to concern for delays.
STUDY FUNDING/COMPETING INTEREST(S): This study was supported by departmental research funding within the University of
California, San Francisco Department of Obstetrics, Gynecology and Reproductive Sciences. There are no conflicts of interest to declare.

Key words: fertility preservation / breast cancer / neoadjuvant chemotherapy / random start ovarian stimulation / treatment delay

neoadjuvant chemotherapy are not yet known to affect oncological out-

Introduction
Chemotherapy for breast cancer has been associated with infertility and
early menopause (Partridge et al., 2007; Letourneau et al., 2011b). Such
detrimental effects on reproductive health have been associated with
decreased quality of life among survivors of breast cancer (Howard-
Anderson et al., 2012). Having the ability to discuss one’s future repro-
ductive potential prior to chemotherapy, as well as the ability to freeze
oocytes or embryos for future use, have been associated with improve-
ments in quality of life (Letourneau et al., 2011a; Deshpande et al., 2015).
Neoadjuvant chemotherapy is now a widely accepted treatment
modality for operable breast cancer. Neoadjuvant chemotherapy
offers the benefit of potentially improved cosmesis and provides an
opportunity to assess histologic tissue response to chemotherapeutic
agents (Ahn et al., 2015). Although adjuvant chemotherapy remains
the most common breast cancer treatment, neoadjuvant chemother-
apy is becoming more popular, with an estimated ten percent of
chemotherapy now given in the neoadjuvant setting (Graham et al.,
2015). The adjuvant treatment setting allows for more time to achieve
oocyte or embryo cryopreservation because diagnosis is followed by
surgery, post-surgical recovery, and, finally, chemotherapy (Baynosa
et al., 2009). In the neoadjuvant setting, however, diagnosis immedi-
ately precedes chemotherapy, creating an apparent time pressure to
complete the fertility preservation (FP) process. The American Society
of Clinical Oncology recommends referral to a fertility specialist prior
to gonadotoxic cancer treatment, such as neoadjuvant chemotherapy,
in reproductive age women (Loren et al., 2013). The increased popu-
larity of neoadjuvant chemotherapy necessitates a focus on how to
most efficiently complete FP consultation and oocyte retrieval while
minimizing cancer treatment delays.
A 2009 study demonstrated that conventional start ovarian stimula-
tion, which can take up to 4–6 weeks to complete a single cycle of egg
or embryo freezing, because the ovarian stimulation start is timed with
the onset of next menses, does not appear to delay the onset of adju-
vant chemotherapy for breast cancer (Lohrisch et al., 2006; Baynosa
et al., 2009; Gagliato et al., 2014). Over the last several years, however,
there have been significant advances in ovarian stimulation techniques in
an urgent setting, with studies showing that stimulations can start at any
random point in the menstrual cycle with equal outcomes (Cakmak
et al., 2013; von Wolff et al., 2016). Consequently, without the need to
wait for the onset of next menses, egg or embryo cryopreservation can
technically be accomplished within 2 weeks of consult. In the setting of
neoadjuvant chemotherapy treatment, this method of ‘random start’
ovarian stimulation may minimize delays. While delays in the initiation of
comes, a perceived delay in therapy can cause distress for patients and
providers (Gold et al., 2016).
Starting in 2011, all patients in our FP center who planned to
undergo neoadjuvant chemotherapy were treated with random start
ovarian stimulation if they chose to freeze oocytes or embryos. To
determine whether random start ovarian stimulation is associated with
delays in the onset of neoadjuvant chemotherapy, we performed a
record review on this population.
Materials and Methods
We performed a cross-sectional study. All study procedures were
approved by University of California, San Francisco (UCSF) Committee on
Human Research.
FP consultation
Our patients were referred from regional oncology centers for FP consult-
ation after they were diagnosed with breast cancer. At the initial FP con-
sultation, we assessed ovarian reserve by measuring antral follicle count
(AFC). Using a combination of AFC, patient age and population-based
expectations for post-chemotherapy reproductive health outcomes,
patients were informed of an estimate of their post-chemotherapy repro-
ductive potential (Letourneau et al., 2011b). Some patients then decided
to undergo ovarian stimulation for FP while some did not. Every patient
who chose to freeze eggs or embryos underwent a random start,
antagonist-based, ovarian stimulation cycle and egg retrieval. All patients
with estrogen receptor positive cancer received Letrozole or Tamoxifen
for estrogen modulation during ovarian stimulation.
Study population
An electronic chart-review was performed to select all patients from our
clinic who had undergone evaluation for FP from January of 2011 through
April of 2017. January of 2011 was chosen as the beginning of the study
because that was when we began to routinely utilize random start ovarian
stimulation. Inclusion criteria included being age 18–45 years old at FP con-
sultation, having a recent non-metastatic breast cancer diagnosis with
upcoming neoadjuvant chemotherapy, and having been seen for FP con-
sultation. Patients were excluded if they had metastatic breast cancer or
did not ultimately undergo neoadjuvant chemotherapy. We categorized
patients who were seen for FP consultation into those who did undergo
ovarian stimulation to cryopreserve oocytes or embryos and those who
did not. We recorded various demographic and cancer history characteris-
tics for each patient. Clinical cancer stage was defined by tumor size and
node status on diagnostic imaging.
Fertility preservation and time to chemotherapy 2125

Six dates were recorded for each patient: date of breast cancer diagno-
sis, date of referral by the oncology team for FP consultation, date of FP Table I Patient demographics and cancer history.
consultation, date of ovarian stimulation start, date of oocyte retrieval, and
Underwent Declined P-value
date of chemotherapy start. By calculating the difference between the
ovarian ovarian
dates listed above, we created seven elapsed time metrics to evaluate vari- stimulation stimulation
ous phases of FP care from diagnosis to neoadjuvant chemotherapy start: N = 58 N = 29
........................................................................................
• Diagnosis to FP referral = Date of referral by the oncology team for FP
Age in years 33.7 ± 4.5 37.1 ± 4.4 0.001
consultation minus Date of breast cancer diagnosis (defined by biopsy (mean + SD)
date).
AFC (mean + SD) 16.5 ± 9.9 13 ± 11.8 0.15
• Referral to FP consult = Date of FP consultation minus Date of referral
by the oncology team for FP. Nulliparous para (%) 81 72 0.346
• FP consult to ovarian stimulation start = Date of first ovarian stimulation Estrogen receptor 64 68 0.711
cycle start minus Date of FP consultation. positive (%)
• First ovarian stimulation duration = Date of first ovarian stimulation Her2 positive (%) 46 48 0.872
oocyte retrieval minus Date of first ovarian stimulation cycle start. Clinical stage (%)
• Time between first and second ovarian stimulation = Date of second Stage 2 66 72 0.516
ovarian stimulation cycle start minus Date of first ovarian stimulation
Stage 3 34 28 0.623
oocyte retrieval.
• Second ovarian stimulation duration = Date of second ovarian stimula- AFC, Antral Follicle Count.
tion oocyte retrieval minus Date of second ovarian stimulation cycle
start.
• Last contact with FP clinic to chemo = Date of chemotherapy start
minus Date of last oocyte retrieval (or Date of FP Consultation, if Table II Ovarian stimulation cycle characteristics.a
patient did not undergo ovarian stimulation).
Cycle parameter Mean ± SD N = 58
........................................................................................
Statistical analysis AFC 16.5 ± 9.9
Electronic medical record data were extracted and de-identified. Statistical Cycle length (days) 12.4 ± 1.7
analyses were performed using Stata version 14 (Stata Corp, College Total gonadotropin (IU) 2368 ± 747
Station, TX). Statistical significance was defined by two-sided P-values of Peak estradiol on trigger day (pg/ml) 1560 ± 1322b
<0.05. T-tests and proportion tests were used to compare demographic
Oocytes collected 21.1 ± 11.3
and cancer history characteristics. Descriptive statistics and t-tests were
used to compare time-points from cancer diagnosis to chemotherapy. We Day 3 embryos frozen (24 patients) 10.3 ± 5.1
identified cancer history or demographic characteristics that were signifi- a
These numbers reflect each patient’s first ovarian stimulation cycle. Two patients
cantly different (P < 0.05) between those who did and did not undergo underwent a second ovarian stimulation cycle.
b
ovarian stimulation. These significantly different characteristics were then This estradiol value reflects all women in the study. Women with Estrogen
included in a general linear model to evaluate for confounding upon aver- Receptor positive breast cancer had lower peak estradiol (due to Letrozole use)
with an average of 889 ± 655 pg/ml at peak on the day of trigger. We generally
age time from diagnosis to chemotherapy.
titrate letrozole throughout the cycle to keep estradiol levels below 500 pg/ml. The
average peak estradiol levels were higher than 500 pg/ml in the Estrogen Receptor
positive breast cancer group because we used Tamoxifen for estrogen modulation
Results in some cycles, rather than Letrozole.

Eighty-nine patients met inclusion criteria. Complete chemotherapy

and FP records were available for 87 (98%) of these patients. Fifty-
eight women (67%) underwent at least one cycle of ovarian stimula-
tion for FP. Two of the 58 women underwent two cycles of ovarian
stimulation prior to chemotherapy start. Twenty-nine women (33%)
did not undergo ovarian stimulation.
Women who underwent ovarian stimulation were younger than
women who did not (33.7 ± 4.5 versus 37.1 ± 4.4 years, P = 0.001).
Women who did and who did not undergo ovarian stimulation were
similar in terms of: AFC, prior parity, clinical cancer stage and hor-
mone receptor status (Table I). Patients referred from within our uni-
versity system underwent ovarian stimulation 76% of the time,
whereas that those referred from a regional cancer center outside the
university did so at lower rate of 52% (P = 0.019). Referral from out-
side the university system did not result in longer delays from cancer
diagnosis to FP consultation or from last visit with an FP provider to
the start of chemotherapy (Supplementary Table SI).
Those who underwent ovarian stimulation had an average of 21.1 ±
11.3 oocytes retrieved (Table II). Ovarian stimulation lasted an
average of 12.4 ± 1.7 days and was associated with average peak
estradiol levels of 1560 ± 1322 pg/ml. Women with Estrogen
Receptor positive breast cancer had lower peak estradiol, given
Letrozole use, with an average of 889 ± 655 pg/ml. Twenty-four
women chose to freeze Day 3 embryos and had an average of 10.3 ±
5.1 embryos frozen.
Those who did not undergo ovarian stimulation were referred for
FP consultation an average of 9 days later than those women who did
undergo ovarian stimulation (17.9 ± 15.3 versus 9.4 ± 6.8 days, P <
0.001; Table III). The time from initial FP consult to chemotherapy
start was slightly shorter in the group that did not undergo ovarian
stimulation (17.7 ± 13 versus 25.2 ± 8.4 days, P = 0.002). During this
time from FP consult to chemotherapy start, women who did undergo
ovarian stimulation spent an average of 3.9 ± 4.9 days preparing to
start ovarian stimulation and another 12.7 ± 2.5 days undergoing ovar-
ian stimulation. However, after completing their care with the FP clinic,
women who underwent ovarian stimulation started chemotherapy
within an average of 8.4 ± 6.2 days. This is 9 days shorter than the
2126 Letourneau et al.

time from last FP clinic visit (their initial FP consultation) to chemother-
apy start among those who did not undergo ovarian stimulation
(8.4 ± 6.2 versus 17.7 ± 12 days, P < 0.001) (Table III). While the
average time from diagnosis to chemotherapy is similar in both groups,
individuals appear to differ in the amount of time spent in various
phases of FP care (Fig. 1).
Overall, the average time from cancer diagnosis to chemotherapy
was similar between the group that did undergo ovarian stimulation and
those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672;
Table III). This relationship continued to lack a significant difference after
controlling for the effect of age and referral center (inside or outside of
the same university) (Linear model coefficient = −1.82, P = 0.615).

Table III Average periods of time elapsed.

Elapsed time (days) Underwent ovarian Declined ovarian P-value

stimulation n = 58 stimulation n = 29
.............................................................................................................................................................................................
Cancer diagnosis to chemotherapy 38.1 ± 11.3 39.4 ± 18.5 0.672
Cancer diagnosis to FP referral 9.4 ± 6.8 17.9 ± 15.3 <0.001
FP referral to FP consultation 3.5 ± 2.5 3.8 ± 2.9 0.587
FP consultation to ovarian stimulation start 3.9 ± 4.9 N/A
Ovarian stimulation lengtha 12.7 ± 2.5 N/A
Last contact with FP clinic to chemotherapy start 8.4 ± 6.2 17.7 ± 12 <0.001
a
Includes two women who underwent two cycles of ovarian stimulation.
FP, fertility preservation. Data are mean ± SD.

Figure 1 The timeline from cancer diagnosis to chemotherapy with the lengths of various phases of FP inlayed for each patient. The upper cluster in
the graph describes those who underwent ovarian stimulation while the lower cluster describes those who did not. While the average time from diag-
nosis to chemotherapy is similar in both groups, individuals differ in the amount of time spent in various phases of FP care. These various phases of care
are defined in the color-coded key above (more detailed descriptions of the time-points in the key are available in the Materials and Methods section).
FP, fertility preservation.
Fertility preservation and time to chemotherapy
The average time spent in the ovarian stimulation process was 12.7 ±
2.5 days, including two patients who underwent a second cycle of
ovarian stimulation. The first cycle of ovarian stimulation, amongst all
who underwent ovarian stimulation, lasted an average of 12.4 ± 1.6
days. Two patients underwent a second cycle of ovarian stimulation
due to diminished ovarian reserve. In order to better meet their future
family-building goals, a second cycle was attempted in each case. The
average time from the first cycle’s oocyte retrieval to the second
cycle’s ovarian stimulation start was 4.5 ± 6.4 days. The average length
of the second cycle was 9 ± 7.1 days. The time from diagnosis to
chemotherapy in the two patients who underwent two cycles was
43.5 ± 10.6 days.
Discussion
In the neoadjuvant setting, where time to chemotherapy is shortened
as compared to the adjuvant setting, ovarian stimulation can be suc-
cessfully performed. Using random start ovarian stimulation, we were
able to complete ovarian stimulation and oocyte retrieval within
approximately two weeks. Among women who complete FP consult-
ation, random start ovarian stimulation is unlikely to delay time to initi-
ation of neoadjuvant chemotherapy start.
We observed that patients in the ovarian stimulation group and the
no ovarian stimulation group each took an average of 5–6 weeks to
start neoadjuvant chemotherapy. Naturally, this timing may reflect
unmeasured aspects of care within our referral network, including:
patient decision-making time, the number of second- and third opi-
nions sought, and varying extents of pre-treatment imaging and biop-
sies (Bleicher et al., 2012). Such aspects of care may also explain, at
least in part, why women who did not undergo ovarian stimulation still
took 18 days to start chemotherapy after their FP consult. In other
words, chemotherapy may not have started immediately because their
cancer work-up and oncology plan was being completed. Some time is
inherently bound to pass as patients come to understand their diagno-
sis and become comfortable with their oncology treatment plan. So, a
window appears to remain for ovarian stimulation to be conducted
without significant treatment delays.
There are few studies examining the importance of the time interval
from diagnosis to neoadjuvant chemotherapy start, and no prospective
trial can ethically subject patients to intentional delays to determine a
threshold for harm (Bleicher et al., 2012). Data from the California
Cancer Registry shows no decrease in 5-year survival among those
who began neoadjuvant chemotherapy up to 6 weeks post-diagnosis
(Smith et al., 2013). Currently unpublished data reported at the 2016
American Society of Clinical Oncology (ASCO) meeting showed that a
delay of greater than 9 weeks between diagnosis and neoadjuvant
chemotherapy initiation is associated with a decrease in 5-year overall
survival (86% versus 81%) (Sanford et al., 2016). In the ASCO meeting
report, the median time from diagnosis to neoadjuvant chemotherapy
start was ~5 weeks. In the California Cancer Registry study mentioned
above, the median time from diagnosis to neoadjuvant chemotherapy
was 3–4 weeks. The average time to neoadjuvant chemotherapy start
in our study of 5–6 weeks was slightly longer than the two previously
mentioned studies. This slight increase in time from diagnosis to
chemotherapy could be related to unmeasured factors in this repro-
ductive age, urban population, such as multiple consultations and vari-
able decision time regarding cancer treatment options. There are no
data, however, to suggest that this difference would affect cancer
2127
outcomes. Nonetheless, as patients, oncologists, and FP providers are
eager for chemotherapy to begin, and as the future could call for a
push for an earlier onset of chemotherapy, future work should con-
tinue to be aimed at making the FP process as efficient as possible.
We reported on patients who underwent random start ovarian
stimulation. The median time from FP referral to oocyte retrieval was
32 days in the previously mentioned conventional start study in the
adjuvant setting (Baynosa et al., 2009). Using random start ovarian
stimulation, our time from FP referral to oocyte retrieval was 12 days
shorter than the in the adjuvant chemotherapy study, which used con-
ventional start ovarian stimulation. Additionally, for two of the
patients, we were able to complete two random start ovarian stimula-
tion cycles, without significant delays in chemotherapy initiation.
While random start is not a conventional way to stimulate infertility
patients, there have been several studies to support its efficacy.
Previous work in our center has examined ovarian stimulation out-
comes between random start and conventional start ovarian stimula-
tion. This work showed similar total oocyte yields, mature oocyte
yields, and fertilization rates between conventional start and random
start (Cakmak et al., 2013). Recently, others have also noted similar
outcomes after initiating ovarian stimulation during any phase of the
menstrual cycle, supporting the concept of random start ovarian
stimulation (von Wolff et al., 2016).
While the patients who did undergo random start ovarian stimula-
tion had acceptable FP outcomes in this study, we should also focus on
those who did not undergo ovarian stimulation and on those who did
not attend a FP consultation. Those in our study who underwent FP
consult but who did not undergo ovarian stimulation experienced a
longer delay in time from diagnosis to FP referral. Whether this delay
was associated with less patient interest in FP or whether the delay in
referral created an apparent time pressure that led to electing to not
undergo FP is uncertain. Either way, the time from diagnosis to FP
referral likely remains modifiable and improvable. Shortening the time
from diagnosis to FP referral may be especially important among those
women with diminished ovarian reserve, where a double-stimulation
may be possible to help increase oocyte or embryo yield, to allow for
a second cycle without delaying chemotherapy. Encouraging other
healthcare providers, including nurses, social workers and patient navi-
gators, to initiate the FP consult may be one method of shortening the
time from diagnosis to FP referral (Bann et al., 2015). Our study popu-
lation came from regional referral centers and we unfortunately do not
have access to information about which patients were not referred for
FP from many of these centers. However, recent data from Chien
et al. suggests that the average time from diagnosis to neoadjuvant
chemotherapy among those who did not undergo FP consult was 40
days (Chien et al., 2017).
Strengths and Limitations
This study is limited by its retrospective nature and the potential for
selection bias. Such bias could result in unmeasured differences among
those who did and did not undergo ovarian stimulation, in terms of
patients’ and providers’ perceptions of the urgency to start chemo-
therapy. However, the relatively large number of patients and the var-
iety of referral centers from which patients were sent for FP
consultation strengthens this study and may mitigate selection bias.
While FP in the neoadjuvant chemotherapy setting appears safe, more
data from other investigators are needed to corroborate these findings
2128
and to explore the relationship between delay in neoadjuvant chemo-
therapy start and long-term cancer outcomes (Chien et al., 2017).
Until outcomes data support a specific problematic timing threshold,
the reader must make a judgment about whether potential delays in
neoadjuvant chemotherapy are clinically meaningful.
The difference in time from referral to FP consultation may have
influenced patients’ decisions about whether to undergo ovarian
stimulation. There could be many factors, which were unmeasured in
this study, that lead to a delay in time from diagnosis to FP referral and
which may also in turn influence the decision to undergo ovarian
stimulation, including: ongoing oncology work-up and treatment plan-
ning, second and third opinions for oncology and FP care, patient and
provider decision-making about whether to pursue FP, and patients
weighing the cost of FP (which is often not covered by insurance).
Some of these unmeasured factors may have also resulted in a pro-
longed time from last contact with the FP to chemotherapy in the
group that did not undergo ovarian stimulation. Future studies should
focus on the influence of factors, such as second opinions and patient
or provider decision-making, which could affect the timing of chemo-
therapy start in the FP setting. Future studies could also evaluate ran-
dom start stimulation after use of ovarian reserve markers other than
AFC, such as AMH. However, in order to begin random start stimula-
tion as soon as possible after FP consultation, serum lab results that
inform ovarian stimulation regimens should be available promptly. In
the absence of these labs, we view AFC as a timely assessment of
ovarian reserve, which, despite inter-operator variability, does correl-
ate well with oocyte yield and helps to set expectations for patients in
the random start setting (Fleming et al., 2015; Kotanidis et al., 2016;
Moon et al., 2016).
Conclusion
FP is becoming more common and so too is neoadjuvant chemother-
apy. In the neoadjuvant setting, random start ovarian stimulation offers
the advantage of shortened time from initial fertilization preservation
consult to egg retrieval. However, early referral for FP remains para-
mount, as earlier referral may lessen a perceived time pressure for
patients and providers. Among those considering FP in the setting of
neoadjuvant chemotherapy for breast cancer, providers can reassure
patients that random start ovarian stimulation appears unlikely to sig-
nificantly delay the start of their chemotherapy.
Supplementary data
Supplementary data are available at Human Reproduction online.
Acknowledgements
We would like to make a special thanks to our nurses, Elizabeth
Gomes, Cathy Chin-Yu and Audra Katz, who provided patient educa-
tion and ovarian stimulation cycle coordination. Lastly, we thank the
UCSF Department of OB/GYN for their support of this study.
Authors’ roles
J.M.L.’s roles included study design, data collection, data analysis and
manuscript writing. N.S., K.W., E.H. and M.Q.’s roles included data
Letourneau et al.
collection and manuscript writing. T.I.’s roles included study design,
data analysis and manuscript writing. E.M.-L.’s roles included data ana-
lysis and manuscript writing. A.J.C.’s roles included study design, data
analysis and manuscript writing. M.R.’s roles included study design,
data analysis and manuscript writing.
Funding
This study was supported by departmental research funding within the
University of California, San Francisco Department of Obstetrics,
Gynecology and Reproductive Sciences.
Conflict of interest
None declared.
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