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Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 4-9

Oocyte vitrification as a choice of fertility preservation and its role in endometriosis cohort

GG Hospital, Fertility Research and Women’s Speciality Centre, Chennai, India

Date of Submission23-Apr-2021
Date of Acceptance16-Jul-2021
Date of Web Publication17-Dec-2021

Correspondence Address:
Dr. Priya Selvaraj
GG Hospital, Fertility Research and Women’s Speciality Centre, Chennai.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tofj.tofj_3_21

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Endometriosis is being widely diagnosed in women of reproductive age. There often arises a situation which compromises the fecundity of those women with moderate-to-severe endometriosis as it affects the ovarian tissue, lowers ovarian response to stimulation, and may also lead to premature ovarian failure. In order to treat the condition for shifting the living experience of the patients to a better edge, various treatments are being offered. However, surgical interventions are associated with lower ovarian reserve. In endometriosis patients without a male partner, oocyte vitrification can play a vital role. The same can be a choice when there are unforeseen events of azoospermia. The success of oocyte vitrification is dependent on outcome of appropriate treatment protocols followed by technical expertise. This qualitative review has been performed to understand the paradigm of managing the disease and also the role of oocyte vitrification in an endometriosis cohort. An electronic literature search was performed in PubMed/Medline and Google Scholar search engines to retrieve 51 articles that comprised of original articles, short reports, review articles, meta-analysis, and case studies published so far in the relevant field. The search terms used were oocyte vitrification, fertility preservation, endometriosis, endometrioma, infertility, ovarian reserve, and moderate to severe endometriosis. Articles of languages other than English were excluded.

Keywords: Endometriosis, fertility preservation, oocyte vitrification, ovarian reserve, ovarian response

How to cite this article:
Selvaraj P, Selvaraj K, Chandrasekar H. Oocyte vitrification as a choice of fertility preservation and its role in endometriosis cohort. Onco Fertil J 2021;4:4-9

How to cite this URL:
Selvaraj P, Selvaraj K, Chandrasekar H. Oocyte vitrification as a choice of fertility preservation and its role in endometriosis cohort. Onco Fertil J [serial online] 2021 [cited 2023 Jan 27];4:4-9. Available from: https://www.tofjonline.org/text.asp?2021/4/1/4/332639

  Introduction Top

Over the past four decades, assisted reproductive technology (ART) has evolved rapidly offering broad strategies for fertility preservation in young women with oncologic and non-oncologic conditions. It minimizes the burden associated with the disease and ensures the maintenance or preservation of reproductive health, which can be affected by surgical interventions, advancing age, and other metabolic conditions. The incidence of endometriosis is 6–10% in young women of reproductive age. It is prevalent among 20–30% infertile women.[1] The disease is characterized by the presence of endometrial tissue growth outside the uterus, mostly on the ovary and peritoneum.[2],[3] Ovarian endometrioma is a condition which is confirmed when a cystic mass of diameter greater than 1 cm, with a regular margined thick wall, is encountered with homogeneous low echogenic fluid content in the absence of papillary proliferation.[4] Although it is a silent threat in asymptomatic conditions, many women with endometriosis undergo severe pelvic pain, dyspareunia, and dysmenorrhea.[3],[5] It is considered that ovarian endometrioma may turn detrimental to the ovarian reserve; this paves way to believe that the condition often causes infertility, but we are yet to unfold the relationship associated with the same. It is well understandable that women with endometriosis struggle through a tumbling social life.[6],[7] Hence, the recommendation to cryopreserve oocytes is growing stronger as fertility preservation is widely established in the current era.[8] This is a qualitative review constructed from a bird’s eye view with the aim to understand the role of oocyte vitrification as a management approach for women with endometriosis.

  Materials and methods Top

An electronic literature search was performed in PubMed/Medline and Google Scholar search engines to retrieve original articles, short reports, review articles, meta-analysis, and case studies published so far in the relevant field. The search terms which were used are oocyte vitrification, fertility preservation, endometriosis, endometrioma, infertility, ovarian reserve, and moderate to severe endometriosis. Articles of languages other than English were excluded. An unbiased review was performed using a total of 51 articles.

  Endometriosis and poor oocyte quality Top

Endometriosis increases the volume of peritoneal fluid with a higher concentration of activated macrophages, prostaglandins, interleukin-1, tumor necrosis factor, and proteases. Perhaps, these changes can impose negative effects on the quality of germ cells, embryos, and  Fallopian tube More Detailss. Altered endometrial receptivity and implantation failure may be due to the elevated level of antibodies IgA and IgG in response to the endometriosis.[3] In a review performed by Barnhart et al.[2] in 2002, data from 22 studies were included to perform the meta-analysis. They have noted a greater negative association with endometriosis and reproductive outcomes with a reduction of 35% in the chance to achieve pregnancy using in vitro fertilization (IVF) in women with endometriosis compared with women without such medical condition. Women with severe endometriosis exhibited decrease in pregnancy rate, implantation rate, and lower E2 concentration and decreased number of oocytes retrieved per cycle. Mitochondrial DNAs are present in mitochondria which are essential for cellular energy production. Generally, in humans, there are approximately 105 mitochondria in a normal MII oocyte. The low mtDNA content might lead to poor energy production which results in insufficient oocyte maturation, linked to poor oocyte quality. In a study conducted by Xu et al.,[9] the cytoplasm of oocytes from women with endometriosis was observed with abnormal mitochondria containing small, swollen, blurred vacuoles. The rate of abnormal mitochondria in the endometriosis group increased with a decrease in the number of mitochondria and mtDNA copies. Whereas the control group exhibited normal quantity of mtDNA.

Dating back to 1998, a study was carried out on understanding the effects of endometriomas on oocyte quality, embryo quality, and pregnancy rates in IVF cycles. The study results supported their hypothesis that the presence of endometriomas during an IVF cycle adversely affected the cycle outcome, with an increased rate of early pregnancy loss. Their findings exhibited that patients with endometriosis produced decreased number of oocytes. Though fertilization rates were similar between endometrioma patients and controls, a lower percentage of embryos reaching the four cells or greater cleavage stage among patients with endometriomas was observed.[10] To overcome these hurdles in achieving live births, multiple methods are being used to treat the disease. The choice of treatment which does not affect the fertility factors is still under debate.

  The effects of surgical procedures on ovarian reserve and response Top

Endometriosis is commonly treated with medications, laparoscopic surgery, cauterization, electrocoagulation, and endometrial ablation. As the impact of these approaches on ovarian reserve remains controversial, numerous researches are being carried out in the medical fraternity.

In 2019, Orazov et al.[4] conducted a prospective study with women aged between 24 and 40 years. Patients in group I (n = 50) were facing recurrent unilateral endometriomas, group II (n = 50) were those after surgical treatment of unilateral endometriomas, and control group (n = 30) with tubal factor infertility. They produced a result of decreased number of antral follicles and oocytes in patients of groups I and II when compared with the control group. They also encountered structural changes, displacement of the nucleus envelope, and various indications of degenerative changes in every fourth oocyte retrieved from the ovary-containing endometrioma.

A prospective study conducted by Goodman et al.[5] included 58 women with endometriomas and 58 individuals as control. Anti-Mullerian harmone (AMH) values were significantly lower in women with endometriomas when compared with the control subjects. This study shows that women with endometriosis exhibit baseline AMH values that are 36% lower than women with peritoneal endometriosis and 45% lower than women without laparoscopic evidence of endometriosis and that ovarian cystectomy has a further deleterious effect on ovarian reserve. The decline in women who underwent ovarian cystectomy was 48% in 1 month’s and 28% in 6 months’ time. The risk of ovarian reserve impairment varies broadly between patients undergoing surgery of small unilateral endometriomas and patients with large bilateral cysts.[11] Laparoscopic excisional surgery in women with unilateral endometriomas leads to decreased antral follicle count (AFC) and AMH levels when compared with their pre-operative values.[12] There is a progressive decline in the ovarian reserve following the surgery. It is proposed that both the presence of endometriomas and their excision negatively affect ovarian reserve and are sustained over 6–9 months. Hence, it is prudent to delay surgical excision in nulliparous women.[10]

Cyst wall vaporization is another approach to manage endometrioma; its effect on IVF outcome was studied retrospectively by Doonez et al.[13] in 2000. Vaporization of internal cyst wall did not impair ovarian function in terms of IVF outcome. However, risks of loss of viable ovarian tissue in the process of ovarian endometrioma surgery are high; such risks may be avoided by a laparoscopic technique which leaves the normal residual ovarian cortex intact.

There are other perspectives which act diametrically in contrast to the above-mentioned findings. In a prospective analysis with a study population of 170, the aim was to investigate whether aspiration of ovarian endometrioma before controlled ovarian stimulation improves the prognosis of intracytoplasmic sperm injection (ICSI) cycles. The observation exhibited patients with non-aspirated endometriomas to have lower levels of E2 on the day of human chorionic gonadotropin injection and lower numbers of follicles and metaphase II oocytes compared with those with tubal factor infertility. They concluded that resection of small endometriomas (1–6 cm) may not impose any additional benefits to the ICSI–IVF cycle outcomes.[6] Suzuki et al.[14] performed a retrospective study to evaluate the effect of endometriosis and ovarian endometrioma on IVF outcomes. No statistical differences were recorded among the three groups with regard to fertilization rate, embryo quality, implantation rate, pregnancy rate, and live birth rate. However, the number of oocytes retrieved decreased with the presence of endometriosis even after laparoscopic treatment. Therefore, they concluded that following laparoscopic treatment, an ovarian endometrioma has no negative impacts on the developmental competency.

The ovarian response to controlled ovarian hyperstimulation (COH) and pregnancy rates in patients once treated with laparoscopic cystectomy were similar to those of control patients. Nevertheless, higher dosage of recombinant gonadotropins was needed to achieve a satisfactory COH for IVF-embryo transfer.[15] Another study was also in accordance, stating that there was no difference in ovarian response when comparing patients with endometriosis who underwent laparoscopic ovarian cystectomy with tubal factor infertility individuals.[16] In a retrospective cohort study conducted by D’Hooghe et al.,[17] they concluded that women with moderate-to-severe endometriosis who do not conceive spontaneously after laparoscopic treatment for endometriosis have a higher chance for recurrence. It was also noted that the recurrence rate was higher in those who underwent only intrauterine insemination (IUI) than in those who either underwent IVF or both IUI and IVF. It is reported that ovarian hyperstimulation does not worsen endometriosis-related symptoms in patients undergoing IVF cycles.[18] However, patients require intense supportive care as the incidence of recurrence is high in chronic conditions.

  Vitrification as fertility preservation Top

Cryopreservation is the process in which cells and tissues are preserved for an extended period of time at sub-zero temperature using permeating and non-permeating cryoprotective agents (CPAs). Controlled freezing was followed for a longer period, but ever since vitrification made an advent, the success in ART treatment began growing to new heights. It lowers the risk of ice nucleation and crystallization unlike slow freezing; however, higher concentrations of CPAs are required.[19],[20],[21],[22] The post-thawing survival rate is higher in vitrified oocytes when compared with slow freezing technique and the ultrastructural preservation is good in mature oocytes subjected to vitrification.[23],[24],[25],[26]

Therefore, vitrification is better than slow freezing technique as it also prevents intra-cellular ice crystal formation, which causes damage to the cells.[27] Oocyte vitrification as fertility preservation was generally used for patients undergoing cytotoxic treatments for malignancy, as time unfolds, the technique is now being offered to patients with benign diseases which puts fertility at stake. But there exists a question focussing on whether oocyte vitrification should be carried out before or after the surgical management of endometriosis.[11],[28],[29]

The ovarian reserve in patients with endometriosis is believed to be lesser than those of same age without endometriosis. A study shows that women with history of previous surgery for endometrioma leads to poorer ovarian response to COH; hence, pre-operative oocyte vitrification as fertility preservation should be recommended to the patients.[30],[31],[32] Nevertheless, the reproductive outcomes after the usage of post-thaw survived oocytes remain speculative. In a multicenter, descriptive, observational study, oocytes of 485 women with endometriosis were vitrified for fertility preservation. The cumulative live birth rate (n = 124, 49.0%) was higher in patients who did not undergo surgery than in those who underwent unilateral surgery (n = 61, 40.4%) and bilateral surgery (n = 40, 49.3%). The realistic choice in young aged endometriosis patients without a male partner is to avail for oocyte vitrification before undergoing surgery. However, multiple cycles might be essential to aspirate an adequate amount of oocytes as they report low ovarian reserve.[33],[34]

Elizur et al.[35] have published a case report on a 25-year-old nulliparous woman with severe and symptomatic endometriosis and low AFC. Due to lower AFC, the patient was subjected to three cycles of ovarian stimulation and oocyte aspiration. Twenty-one mature oocytes were vitrified as there was no male partner. The cryopreserved oocytes can be used in the future to fulfill her desire to conceive. The number of oocytes retrieved for vitrification has got a positive effect on the chances of achieving pregnancy.[36] A study was performed to draw attention on the vitrification outcomes in women with endometriosis and to compare progestin-primed ovarian stimulation with antagonist protocol. They demonstrated that both the protocols yielded similar number of mature oocytes, hence suggesting oocyte cryopreservation in patients at early stages of endometriosis indicating lower ovarian reserve.[37] The vitrified oocytes exhibited better developmental competency from mature oocyte to blastocyst stage. There were no further obstetrical or neonatal morbidities associated with pregnancy achieved through vitrified oocytes.[38],[39] The implantation rates seem to be on par with the control values when good quality oocytes are vitrified.[40] Hence, the efficacy of oocyte vitrification acts as an adjunct to standard IVF treatment and for elective preservation.[41]

Garcia-Velasco et al.[42] reported 5 years’ experience using oocyte vitrification to preserve fertility for medical and non-medical indications. The overall non-oncologic patients were 560, out of which 38 patients were facing endometriosis. They underwent COH and the oocytes were vitrified. Only five patients returned for trying to achieve pregnancy. However, only the overall survival rate (84.8%) of post-thawed oocytes for non-oncologic patients is available in this study. In a review presented by Son et al.,[43] they emphasize the practice of vitrifying in vitro maturation oocytes for patients who are in danger of losing their ovarian function due to oncologic or non-oncologic medical conditions. However, Cohen et al.,[44] in their retrospective study, yielded significantly lower fertilization rate, embryo development, embryo quality, pregnancy, and lower live birth rates in in-vitro maturation oocyte vitrification. A prolonged administration of gonadotrophin-releasing hormone agonists after vitrification protocol in IVF patients with endometriosis led to high implantation rate, despite a high incidence of prior cycle failure.[45] Dahhan et al.[46] conducted a follow-up study to determine the reproductive choices women make after they have cryopreserved oocytes for medical reasons. It was found that none of the women associated with a medical reason, in the period of 2 years, turned up to use the cryopreserved oocytes in attempting to achieve pregnancy. Instead, they have achieved pregnancy without the usage of the cryopreserved oocytes.

The candidates those seeking for fertility preservation must be counseled carefully by giving out detailed information including the cost breakouts of the process.[47] A familial history of premature ovarian insufficiency, body mass index, alcohol consumption, smoking, and biomarkers of ovarian reserve should be additionally evaluated.[48] Embryo cryopreservation grabs the central importance in IVF. However, in single women struggling from malignant and benign diseases, oocyte vitrification will play a prime role in aiding to achieve pregnancy, despite their medical conditions in future.[49],[50] Women at young age associated with illness which could possibly put their fecundity at stake should be encouraged to vitrify oocytes as fertility preservation to avoid age-related fertility decline in the future.[51]

In conclusion, endometriosis is associated with lowered ovarian reserve, poor quality of oocytes, and/or diminished ovarian response and infertility. Hence, this non-oncologic medical condition in young women might become an indication for fertility preservation. Oocyte vitrification can be a potential choice in single women without a male partner and also in situational azoospermia. Therefore, we recommend oocyte vitrification as a choice of fertility preservation prior to any surgical interventions as per the clinicians’ decisions. This review contributes information which can be used to counsel endometriosis patients in their reproductive age. However, this qualitative review was performed with limited articles as there is a scant in the number of studies available on oocyte vitrification and fertility preservation associated with endometriosis.

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Conflicts of interest

There are no conflicts of interest.

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