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\title{Spontaneous Pregnancy After Fertility-Sparing Surgery and Adjuvant
Chemotherapy for Advanced Pure Dysgerminoma: A Case Report}



\author[1]{Goksu Goc}%
\author[1]{Alida Goc}%
\author[1]{Gezim Kastrati}%
\author[1]{Dardan Baftiu}%
\author[2]{Fisnik Kurshumliu}%
\affil[1]{American Hospital Kosovo}%
\affil[2]{Universiteti i Prishtines Fakulteti i Mjekesise}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\textbf{1 Introduction}

Malignant ovarian germ cell tumor (MOGCT), a rare form of ovarian
malignancy, predominantly affects adolescents and young women of
reproductive age {[}1, 2{]}. This group of ovarian cancers includes
various subtypes, including dysgerminoma, yolk sac tumors, embryonal
carcinoma, non-gestational choriocarcinoma, mixed germ cell tumors, and
immature teratomas, each with distinct characteristics {[}3-5{]}.
Dysgerminoma, akin to male seminoma, represents the most prevalent
histological variant and immature teratoma and is associated with
relatively high bilaterality rates {[}4, 6, 7{]}.

Platinum-based chemotherapy regimens have proven effective in extending
survival and preserving fertility {[}1, 8{]}. Given the chemosensitivity
of these tumor cells, fertility-sparing surgery (FSS) has become a
preferred treatment approach, particularly in patients desiring to
preserve their reproductive capability. FSS, which involves complete
staging and the preservation of at least the uterine corpus and a
portion of one ovary, has emerged as the primary treatment modality in
patients with early-stage MOGCT {[}8-10{]}. However, a couple of studies
in which the potential risks of FSS use have been extensively discussed
have stated that FSS use can be justifiable in advanced-stage MOGCT
patients {[}10, 11{]}.

Menstrual and reproductive outcomes in patients who survived MOGCT are
reportedly similar to those of age-matched healthy women {[}1, 12{]}.
Ovarian function is typically restored following three or four cycles of
platinum-based therapy {[}12{]}. However, fertility rates vary
significantly, including among patients with advanced MOGCT {[}2, 8,
11{]}.

In this context, in this case study, an advanced MOGCT patient who
underwent complete staging and was treated with FSS coupled with
adjuvant cisplatin-based chemotherapy and still achieved spontaneous
pregnancy is presented.

\textbf{2 Case Presentation}

A 23-year-old woman presented with a 6-month history of abdominal
distention and a progressive increasing palpable mass in the lower
abdominal quadrants. At the time of admission, the size of the mass was
equivalent to the swelling in a six-month-pregnant woman. Her personal
and familial medical history was unremarkable.

Her physical examination revealed a firm, smooth, and painless palpable
mass in the right lower quadrant. Ultrasonography revealed a solid right
adnexal mass with a diameter of 20 cm, accompanied by mild
hydronephrosis on the right side. The left ovary and uterus appeared
normal.

Subsequent computed tomography revealed a pelvic mass with a diameter of
22 cm, characterized by an indistinct border between the uterus and
pelvic sidewalls. There was also evidence of right ureteral displacement
(Figure 1a and 1b). Laboratory tests measuring alpha-fetoprotein,
carcinoembryonic antigen, and cancer antigen 125 (CA125) levels did not
reveal any abnormal results.

Following the diagnosis of a right ovarian mass, the patient underwent
surgical exploration via laparotomy. Consequently, a 22 cm right ovarian
mass with external projections, moderate ascites, and peritoneal
implants were observed intraoperatively (Figure 2a and 2b). The
remainder of the abdominal cavity appeared normal, and ascitic fluid was
sampled for cytological examination. Intraoperative cytological frozen
analysis of the tumor revealed malignant cells of the germinal nature.
Right salpingo-oophorectomy was performed for mass excision, and a
biopsy was taken from the left ovary, which appeared more prominent than
average. Excision of all tumoral implants, pelvic and paraaortic lymph
node dissection, and omentectomy were also carried out. No
intraoperative frozen section examination was performed. The patient
received a total of 11 units of transfused erythrocytes, eight
intraoperatively and three postoperatively, with no postoperative
complications. She was discharged on the fifth day after the surgery.

The final histopathological examination revealed a pure dysgerminoma
with multiple lymph node involvement and omental and peritoneal
metastases. Accordingly, she was diagnosed with FIGO (International
Federation of Obstetrics and Gynecology) 3AMOGCT, indicating that the
cancer has spread to the serosa of the uterus and/or the tissue of the
fallopian tubes and ovaries but not to other parts of the body.
Subsequently, the patient was administered BEP (bleomycin, etoposide,
and cisplatin) chemotherapy. She provided a complete clinical and
radiological response after four cycles of BEP. She was followed up
semi-annually during the first year and then annually for the next five
years with no signs of recurrence.

The initial examinations, including hysterosalpingography, which were
performed due to the patient's desire to have children, indicated the
normal functioning of the left salpinx. She had regular menstrual cycles
occurring every 30 days and lasting 4--5 days. Nevertheless, she
underwent in-vitro fertilization since she could not get pregnant. The
first attempt yielded only one mature oocyte with no fertilization. The
second attempt yielded two oocytes, one successfully frozen at the
blastocyst stage. However, before carrying out the transfer procedure,
spontaneous pregnancy occurred. The patient experienced an uneventful
pregnancy and gave birth to a healthy baby girl, during which ligation
of the left uterine artery was performed to manage postpartum uterine
atony.

\textbf{3 Discussion}

The favorable fertility outcome in the case presented herein indicates
that FSS with adjuvant BEP chemotherapy may be a reliable treatment
alternative in patients with advanced dysgerminoma who desire to
preserve their fertility. However, large-scale studies are needed to
validate the safety and feasibility of using this approach in
advanced-stage patients.

Post-treatment pregnancy rates in patients who survived MOGCT are
influenced by a range of sociodemographic and clinical factors,
including age and desire for future motherhood {[}4{]}. Solheim \emph{et
al.} {[}1{]} reported an encouraging 87.2\% post-treatment pregnancy
rate in patients who survived MOGCT attempting to get pregnant.
Similarly, Chu \emph{et al.} {[}2{]} reported that 85.4\% of the MOGCT
patients with planned pregnancies had successful delivery.
Tamauchi\emph{et al.} {[}13{]} reported that 40.0\% of the 105 MOGCT
patients who underwent FSS became pregnant after surgery, and 38.1\% had
successfully given birth, accounting for 95.2\% of the patients who
desired to become pregnant. On the other hand, there are also studies
that reported relatively lower pregnancy and childbirth rates in this
patient group {[}4, 14, 15{]}.

The discrepancies between reported pregnancy rates in this patient
population may be due to the fact that all patients were taken into
account in some studies, and only patients with pregnancy plans were
taken into account when calculating the pregnancy rate in others. The
lack of fertility evaluation in all patients included in the studies and
the differences in follow-up periods and evaluated number of pregnancies
may also have contributed to the discrepancies between reported
pregnancy rates in this patient population {[}12{]}. In sum, independent
risk factors predicting pregnancy outcomes remain controversial due to
inconsistencies between relevant studies available in the literature.
Large-scale studies are needed to identify the independent risk factors
that can predict pregnancy outcomes.

The number of cisplatin-based chemotherapy cycles and cumulative doses
of chemotherapeutics reportedly impact reproductive and sexual functions
{[}1, 16{]}. Several studies found a correlation between having three or
fewer cisplatin-based chemotherapy cycles and higher fertility rates
{[}1, 4{]}. In contrast, our patient achieved spontaneous pregnancy
despite undergoing four cycles of chemotherapy. Similarly,
Ghalleb\emph{et al.} {[}11{]} reported three full-term natural
pregnancies following FSS and six cycles of chemotherapy in MOGCT
patients featuring a seminomatous component with an advanced-stage yolk
sac tumor.

FSS has been asserted as the primary treatment modality in patients with
early-stage (FIGO stages I and II) MOGCT {[}4, 8, 13, 15, 17{]}.
However, considering that most cases included in these studies were at
an early stage, it can be argued that they could not accurately
represent real-world data. Husainiet \emph{et al.} {[}14{]} reported
32\% as the pregnancy rate in patients with pure dysgerminoma, 33.8\% of
whom had FIGO stage III disease, indicating 87.5\% of the patients who
have been trying to get pregnant became pregnant. A study conducted in
Iran {[}12{]} reported the delivery rate as 73\% in 26 patients who have
been trying to become pregnant, approximately half of whom had FIGO
stage III disease. The fact that our patient with FIGO stage III disease
also gave a successful delivery supports the idea that many
advanced-stage MOGCT patients can achieve pregnancy after being treated
with FSS coupled with adjuvant chemotherapy.

\textbf{4 Conclusion}

In the literature, FSS has been asserted as the primary treatment
modality in patients with early-stage MOGCT. In addition, age, desire to
conceive, number of chemotherapy cycles, and cumulative doses of
chemotherapeutics have been reported as major factors affecting
pregnancy rates in patients who survive MOGCT. However, this case study
demonstrated the potential for successful fertility preservation and
pregnancy in an advanced-stage MOGCT patient with pure dysgerminoma
treated with FSS and adjuvant chemotherapy, indicating the potentially
favorable outcomes of personalized treatment strategies in patients with
advanced-stage MOGCT.

In the literature, age, desire to conceive, number of chemotherapy
cycles, and cumulative doses of chemotherapeutics have been reported as
major factors affecting pregnancy rates in patients who survive MOGCT.
Nevertheless, large-scale studies are needed to verify the safety and
feasibility of personalized treatment approaches in this patient
population.

\textbf{Data availability:} Data presented in this study are available
from the corresponding author or first author on reasonable request.

\textbf{Acknowledgment:} The authors disclose that no external funding
or financial support was provided for this study. The open-access
publication fee of the article also is self-funded.

\textbf{Ethics Statement:} Informed consent was signed by the patient,
and all identifiable data has been anonymized wherever possible in
compliance with the Helsinki Declaration and local clinical research
regulations (American Hospital Kosovo, Protocol \# 416, Sept 2 2022)

\textbf{Consent Statement:} Written informed consent was obtained from
the patient to publish this report in accordance with the journal's
patient consent policy

\textbf{Conflict of Interest:} The authors declare that they have no
conflicts of interest.

\textbf{4 References}

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\end{enumerate}\selectlanguage{english}
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