Fertility preservation for ovarian or uterine cancer patients with reference to assisted reproduction technology

Surgical intervention

Fertility preservation in women of reproductive age is more complicated than that of in men. Surgical interventions such as ovariopexy or ovarian transposition may help to retain the reproductive function of women with cancer if radiotherapy is the only mean of treatment (Bisharah and Tulandi, 2003).^[10] Attempts were made to cryopreserve whole ovary after laparoscopic ovariectomy (Jadoul et al., 2007).^[11] Cryopreservation of ovarian cortex prior to cancer therapy and transplantation to the patient after the disease is cured are proven to be successful with live birth (Donnez et al., 2004).^[12] Transplantation of cryopreserved ovarian cortex from patients with advanced stage breast cancer may be safe and may not reintroduce the disease as shown in mice models (Luyckx et al., 2013).^[13]

Controlled ovarian hyperstimulation (COH)

COH with cryopreservation of oocytes or embryos has been endorsed as the most suitable way of fertility preservation in women with cancer (American Society for Reproductive Medicine, ASRM, Committee Opinion, 2013).^[14] Cryopreservation by vitrification techniques yields high survival rates for oocytes and embryos. However, to achieve successful live birth through cryopreserving oocytes or embryos, at least eight oocytes are required for patients aged <38 and more than eight oocytes in patients aged >38 (Rienzi et al., 2012)^[15] which could be obtained by COH. COH with gonadotropins has a potential risk in estrogen-sensitive cancers and also it is time-consuming, where patients with ovarian or uterine cancer may have very short time before cancer therapy. Using aromatase inhibitors such as Letrozole for ovarian stimulation to cryopreserve embryos has been most widely accepted for cancer patients (Lee et al., 2006; Oktay et al., 2010).^[4,16] Ovarian tissue cryopreservation followed by COH with agonist or antagonist to cryopreserve oocytes has been reported (Dolmans et al., 2014).^[17] However, cryopreservation of embryos for fertility preservation requires the patients to have a male partner. In the absence of male partner, patient has to cryopreserve oocytes. COH also poses potential risks with elevated levels of estradiol in hormone-sensitive cancers (Oktay et al., 2010).^[16]

Fertility preservation in patients with cancer of uterus or ovaries

COH is applicable mostly in patients with cancers of non-reproductive organs. When cancer occurs in reproductive organs such as uterus or ovaries, generally, total hysterectomy with bilateral salpingo-oophorectomy is carried out. Hence, patients become totally infertile. As mentioned earlier, these patients are not recommended for COH due to shortage of time and potential risks of using gonadotropins for ovarian stimulation (Lobo et al., 2005).^[18] Ovarian tissue cryopreservation may not be an option due to the risk of reintroducing multi-foci neo-carcinogenesis by transplantation of cryopreserved ovarian tissue (Cadron et al., 2007).^[19] Ultrasound-guided collection of oocytes. From ovary for in vitro maturation (IVM) and cryopreservation also has a risk of spreading the disease at the time of puncture of follicles. Considering the above-mentioned risks, these patients are left with almost no options to preserve their fertility. Harvesting oocytes from surgically removed ovaries and either cryopreserving them or creating embryos after IVM and Intracytoplasmic sperm injection (ICSI) for cryopreservation are the only options available to these patients. Cryopreservation of oocytes may be applicable to patients without male partners, whereas cryopreservation of embryos could be employed only in patients with male partners.

Collection of mature eggs at the time of oophorectomy has been attempted after COH followed by vitrification of these oocytes (Bocca et al., 2011; Fatemi et al., 2011).^[20,21] However, collection of immature oocytes followed by IVM may be a safer approach. Huang et al., (2007)^[22] collected immature oocytes from ovary after oophorectomy and subjected them to IVM. These authors vitrified resulting mature oocytes for future use by the patient. Embryos have been created after warming such vitrified oocytes followed by ICSI (Fadini et al., 2012)^[23] and resulting embryos transferred to uterus, in a patient with ovarian adenocarcinoma. Nonetheless, they did not result in pregnancy. Embryos have been created from fresh oocytes harvested from ovary [Figure 1] followed by oophorectomy after IVM and ICSI in patients with endometrial carcinoma (Revel et al., 2004)^[24] and advanced ovarian cancer (Prasath et al., 2008; Prasath et al., 2014)^[25,26] as these patients had male partners at the time of oophorectomy. The embryos [Figure 2] were frozen as the patients had to undergo cancer therapy. Patients who underwent hysterectomy have to seek surrogacy (Revel et al., 2004; Prasath et al., 2008).^[24,25] Patients, without hysterectomy, may use frozen embryos after completing treatment and cleared of cancer. Our team has published the first report on pregnancy and live birth from frozen-thawed embryos obtained from fresh oocytes, harvested from surgically removed ovary, after IVM and ICSI in a patient with advanced ovarian cancer (Prasath et al., 2014) [Table 1].^[26]

Table 1 Comparison of reports on in vitro maturation (IVM) of oocytes obtained from ovary after oophorectomy in uterine and ovarian cancer patients

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Figure 1

Immature oocytes from patient's ovary (Prasath et al., 2008)^[25]

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Figure 2

Four cell embryos from in vitro matured oocytes (Prasath et al., 2008)^[25]

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Source of Support:

Nil

Conflict of Interest:

None declared.