GYNECOLOGICAL ENDOCRINOLOGY
2019, VOL. 35, NO. 4, 298–300
https://doi.org/10.1080/09513590.2018.1531985
IN VITRO MATURATION FOR URGENT FERTILITY PRESERVATION
Successful in vitro maturation for urgent fertility preservation despite hormonal
contraception by continuous progestin application
Roesner Sabine, Hecht Stephanie, Germeyer Ariane and Strowitzki Thomas
Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany
ABSTRACT
ARTICLE HISTORY
We report a unique case of a rare utilization of IVM. This case shows the successful retrieval of immature
oocytes followed by in vitro maturation (IVM) for fertility preservation in a patient undergoing chronic
progestin contraception. A 24-year-old patient with anaplastic astrocytoma requiring chemotherapy with
temozolomide for 12 cycles as soon as possible with wish for fertility preservation while using a long acting etonogestrel birth control implant presented in our unit for fertility preservation in May 2017. The
currently used implant should be preserved for further contraception. As the ovaries presented with a
high, pco-like, antral follicle count, IVM was offered; the patient agreed. A transvaginal follicular puncture
in general anesthesia without any hormonal intervention and IVM of gained oocytes was performed. As
the patient actually had no spouse, she decided to freeze unfertilized metaphase II stage oocytes (MII).
Thirteen oocytes were obtained, eight of them could be matured and cryopreserved. IVM could be a possibility for fertility preservation in patients with polycystic ovaries when no time is available for stimulation for conventional in vitro fertilization. Even use of continuous progestin application for contraception
is no obstacle.
Received 14 September 2018
Accepted 1 October 2018
Published online 27 November 2018
Introduction
Due to increased survival rates of patients with cancer in reproductive age, attention is focused on the chance of getting pregnant after the potential gonadotoxic chemotherapy or radiation
therapy for these patients. Meanwhile standards for fertility preservation are established, e.g. ovarian stimulation and cryopreservation of unfertilized and fertilized oocytes, cryopreservation of
ovarian tissue, GnRH-antagonists, transposition of the ovaries
and combinations of these techniques [1–4]. Depending on the
actual situation of the patient, one or a combination of these
methods can be offered. As stimulation for in vitro fertilization
(IVF) is the best therapy because of long experience in infertility
treatment, it should be offered in all cases, where no contraindications are present. However, stimulation for IVF is often not
feasible in patients who need chemotherapy without delay due to
the necessary time for ovarian stimulation. After the introduction
of luteal phase protocols, stimulation for IVF can be initiated in
any phase of the menstrual cycle [5], therefore, important time
saving is feasible. Meanwhile, good efforts are made with cryopreservation of ovarian tissue, a possibility for urgent fertility
preservation, when time for stimulation for IVF is unavailable [6–8].
An additional method for short-term fertility preservation is
in vitro maturation (IVM) for patients with high, pco-like, antral
follicle count (AFC): no or only short-time stimulation is needed
before egg retrieval of immature oocytes is performed [9–13].
Oocyte retrieval for IVM is possible in all phases of the menstrual cycle [14–17]. Immature oocytes were matured and cryopreserved with or without fertilization. Further application of
CONTACT Roesner Sabine
sabine.roesner@med.uni-heidelberg.de
University of Heidelberg, Heidelberg, Germany
ß 2018 Informa UK Limited, trading as Taylor & Francis Group
KEYWORDS
Fertility preservation;
in vitro maturation;
contraception; progestin
IVM is maturation of immature oocytes gained from ovarian
tissue removed during ovariectomy [18–21].
In our department, IVM was established in 2005 and we offer
all methods for fertility preservation in young cancer patients.
Therefore, it is obvious to use IVM for fertility preservation in
selected cases. We would like to report one special case where
we used IVM for fertility preservation in a patient carrying an
etonogestrel birth control implant.
Materials and methods
A 24-year-old patient presented in May 2017 in our unit for
fertility preservation with an anaplastic astrocytoma with
IDH1-R132H-mutation requiring chemotherapy with temozolomide for 12 cycles starting as soon as possible. She has had no
prior pregnancies and used a long acting etonogestrel birth control implant currently, which was inserted in September 2016.
Due to this continuous progestin application, a secondary amenorrhea resulted.
After a detailed discussion of the possibilities for fertility preservation, a gynecological examination including ultrasound was
carried out. In this ultrasound examination, the ovaries presented
with an AFC of more than 20 on each side. Follicles were 10 mm
at the most.
During the first appointment at our department, a basal hormonal status was taken. AMH was 7.89 ng/ml (norm 1.3–7.0),
FSH 5.2 U/l (norm 1.0–12.0) and estradiol 39.2 pg/ml
(norm 40–250).
Due to the short time, the implant was inlayed and while a
safe contraception during chemotherapy with temozolomide is
Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls
GYNECOLOGICAL ENDOCRINOLOGY
Table 1. Timetable of events for fertility preservation.
Date
May 5th
May 17th
May 18th
May 19th
May 20th
Event
Diagnosis anaplastic astrocytoma
First consultation in IVF-department
Patients decision for IVM
Transvaginal retrieval of immature oocytes
Confirmation of maturation
Vitrification of MII oocytes
First injection of GnRH-analog
Start chemotherapy
May 24th
May 30th
required, we looked for a way to preserve the implant while taking action for fertility preservation. After counsel in the medical
team, IVM was chosen as a potential method. Advantages and
disadvantages include the chance of not gaining any oocytes during the retrieval, failing of maturation, etc. were explained to the
patient. After one night for consideration, the patient agreed to
perform IVM. As the patient actually had no spouse, she decided
to freeze unfertilized metaphase II stage (MII) oocytes.
Oocyte retrieval was performed in general anesthesia with
a single lumen 17G needle (Cook, Eight Mile Plains, Australia,
K-OSN-1730-B-90) and with a reduced aspiration pressure of
100 mm Hg. During the procedure, the needle was stitched fanshaped through each ovary using continuous aspiration. So,
ovarian tissue was gained of which oocytes were identified
immediately after oocyte retrieval (Cell Strainer, BD Falcon
352350, Heidelberg, Germany) and cultivation was performed for
2–3 h in MediCult IVMV System LAG-Medium (Origio, Berlin,
Germany). Afterwards, the oocytes were put into Final IVMV
Medium (Origio, Berlin, Germany) for 24 h.
Patient’s written approval for publication was given by the
patient’s agreement to be treated.
299
Etonogestrel acts by inhibiting ovulation and modifying the
viscosity of the cervical mucus [23,24]. As IVM needs no hormonal intervention for stimulation before puncture of antral follicles, we do not expect any negative impacts of the implant.
Ben-Haroush et al. reported an IVM during a cesarean section
for fertility preservation, a situation similar to our case because
of elevated progesterone levels during pregnancy [25].
Some studies showed a benefit for maturation of immature
oocytes gained by IVM by priming with hCG [26–28]. On the
other hand, it was possible to mature immature oocytes without
priming with hCG prior to the retrieval [25]. Since we did not
expect any benefit nor of FSH neither of hCG due to the continuous progestin application by the implant, we resigned any
hormonal intervention.
Due to this case, we would recommend that IVM should be
taken in account for fertility preservation especially for patients
with polycystic ovaries and can be performed independently
from simultaneous progestin contraception. We know that such
settings are rare conditions but we hope that we will add some
information to cases where emergency fertility preservation
is mandatory.
Disclosure statement
No potential conflict of interest was reported by the authors.
R
R
References
[1]
[2]
Results
[3]
Thirteen oocytes were found, five reached MII stage after 24 h in
final medium, five reached MI stage and three oocytes were
arrested in germinal vesicle stage. Three of the MI stage oocytes
reached MII stage after further three hours in final medium, two
were still arrested in MI stage after that time. So, in total, eight
oocytes reached MII stage and were cryopreserved by vitrification. The patient has decided to consider other additional methods for fertility preservation depending on the amount of gained
MII oocytes. The obtained oocytes satisfied her expectations. She
therefore abstained from cryopreservation of ovarian tissue, but
started ovarian suppression by GnRH-analog one day after the
retrieval. Chemotherapy was started immediately (Table 1).
[4]
[5]
[6]
[7]
[8]
Discussion
Fertility preservation is an important intervention for young cancer patients who did not complete or even start their family
planning before their illness, requiring potential gonadotoxic
chemotherapy. Therefore, all patients who have not completed
their family planning should have been counseled for fertility
preservation. Many of these patients use hormonal contraception,
some of them by hormonal releasing implants such as
ImplanonV (etonogestrel). Due to urgent start of chemotherapy
and the polycystic ovaries, we decided to offer IVM with consecutive cryopreservation of oocytes as a feasible method for fertility preservation. According to the findings of Sonigo et al., we
expected 10 mature oocytes at least [22].
[9]
[10]
[11]
R
[12]
[13]
von Wolff M, Montag M, Dittrich R, et al. Fertility preservation in
women – a practical guide to preservation techniques and therapeutic
strategies in breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT.
Arch Gynecol Obstet. 2011;284:427–435.
Rodriguez-Wallberg KA, Oktay K. Options on fertility preservation in
female cancer patients. Cancer Treat Rev. 2012;38:354–361.
Rodriguez-Wallberg KA, Oktay K. Fertility preservation during cancer
treatment: clinical guidelines. Cancer Manage Res. 2014;6:105–117.
Martinez F, Andersen CY, Barri PN, et al. Update on fertility preservation from the Barcelona International Society for Fertility
Preservation-ESHRE-ASRM 2015 expert meeting: indications, results
and future perspectives. Fertil Steril. 2017;108:407.
von Wolff M, Thaler CJ, Frambach T, et al. Ovarian stimulation to
cryopreserve fertilized oocytes in cancer patients can be started in the
luteal phase. Fertil Steril. 2009;92:1360–1365.
Dittrich R, Hackl J, Lotz L, et al. Pregnancies and live births after 20
transplantations of cryopreserved ovarian tissue in a single center.
Fertil Steril. 2015;103:462–468.
Donnez J, Dolmans MM. Ovarian cortex transplantation: 60 reported
live births brings the success and worldwide expansion of the technique towards routine clinical practice. J Assist Reprod Genet. 2015;
32:1167–1170.
Jensen AK, Kristensen SG, Macklon KT, et al. Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark.
Hum Reprod. 2015;30:2838–2845.
Oktay K, Buyuk E, Rodriguez-Wallberg KA, et al. In vitro maturation
improves oocyte or embryo cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation.
Reprod Biomed Online. 2010;20:634–638.
Shalom-Paz E, Almog B, Shehata F, et al. Fertility preservation for
breast-cancer patients using IVM followed by oocyte or embryo vitrification. Reprod Biomed Online. 2010;21:566–571.
Huang JY, Chian RC, Gilbert L, et al. Retrieval of immature oocytes
from unstimulated ovaries followed by in vitro maturation and vitrification: a novel strategy of fertility preservation for breast cancer
patients. Am J Surg. 2010;200:177–183.
Chian RC, Uzelac PS, Nargund G. In vitro maturation of human
immature oocytes for fertility preservation. Fertil Steril. 2013;99:
1173–1181.
Sonigo C, Grynberg M. In vitro oocyte maturation for female fertility
preservation. Gynecol Obstet Fertil. 2014;42:657–660.
300
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
R. SABINE ET AL.
Demirtas E, Elizur SE, Holzer H, et al. Immature oocyte retrieval in
the luteal phase to preserve fertility in cancer patients. Reprod
Biomed Online. 2008;17:520–523.
Maman E, Meirow D, Brengauz M, et al. Luteal phase oocyte retrieval
and in vitro maturation is an optional procedure for urgent fertility
preservation. Fertil Steril. 2011;95:64–67.
Grynberg M, Poulain M, le Parco S, et al. Similar in vitro maturation
rates of oocytes retrieved during the follicular or luteal phase offer
flexible options for urgent fertility preservation in breast cancer
patients. Hum Reprod. 2016;31:623–629.
Creux H, Monnier P, Son WY, et al. Immature oocyte retrieval and
in vitro oocyte maturation at different phases of the menstrual cycle
in women with cancer who require urgent gonadotoxic treatment.
Fertil Steril. 2017;107:198–204.
Prasath EB, Chan ML, Wong WH, et al. First pregnancy and live
birth resulting from cryopreserved embryos obtained from in vitro
matured oocytes after oophorectomy in an ovarian cancer patient.
Hum Reprod. 2014;29:276–278.
Segers I, Mateizel I, Van Moer E, et al. In vitro maturation (IVM) of
oocytes recovered from ovariectomy specimens in the laboratory: a
promising “ex vivo” method of oocyte cryopreservation resulting in
the first report of an ongoing pregnancy in Europe. J Assist Reprod
Genet. 2015;32:1221–1231.
Walls ML, Douglas K, Ryan JP, et al. In-vitro maturation and cryopreservation of oocytes at the time of oophorectomy. Gynecol Oncol
Rep. 2015;13:79–81.
Park CW, Lee SH, Yang KM, et al. Cryopreservation of in vitro
matured oocytes after ex vivo oocyte retrieval from gynecologic
[22]
[23]
[24]
[25]
[26]
[27]
[28]
cancer patients undergoing radical surgery. Clin Exp Reprod Med.
2016;43:119–125.
Sonigo C, Simon C, Boubaya M, et al. What threshold values of
antral follicle count and serum AMH levels should be considered for
oocyte cryopreservation after in vitro maturation? Hum Reprod.
2016;31:1493–1500.
M€ak€ar€ainen L, van Beek A, Tuomivaara L, et al. Ovarian function
during the use of a single contraceptive implant: implanon compared
with Norplant. Fertil Steril. 1998;69:714–721.
Simon P, Sternon J. Etonorgestrel (implanon) subcutaneous implant.
Rev Med Brux. 2000;21:105–109.
Ben-Haroush A, Abir R, Sapir O, et al. Aspiration of immature
oocytes during cesarean section for fertility preservation. J Matern
Fetal Neonatal Med. 2017;30:2112–2114.
Chian RC, Buckett WM, Tulandi T, et al. Prospective randomized
study of human chorionic gonadotrophin priming before immature
oocyte retrieval form unstimulated women with polycystic ovarian
syndrome. Hum Reprod. 2000;15:165–170.
Dal Canto M, Brambillasca F, Mignini Renzini M, et al. Cumulus cell–oocyte complexes retrieved from antral follicles in IVM cycles: relationship between COCs morphology, gonadotropin priming and
clinical outcome. J Assist Reprod Genet. 2012;29:513–519.
Zheng X, Wang L, Zhen X, et al. Effect of hCG priming on embryonic development of immature oocytes collected from unstimulated
women with polycystic ovarian syndrome. J Reprod Biol Endocrinol.
2012;10:40.
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