A 38-year-old pregnant patient with a history of renal transplantation sought embryo freezing for fertility preservation and future surrogacy. A cesarean section was performed with direct aspiration of small ovarian follicles. Thirteen identified oocyte-cumulus complexes were cultured. Intracytoplasmatic sperm injection was performed on all mature oocytes and the resulting 4 zygotes were cryopreserved.
Ultrasound-guided transvaginal aspiration of small ovarian follicles and in vitro maturation (IVM) of immature oocytes is an important technology that is gaining acceptance in assisted reproductive technology in selected clinical indications such as in women with polycystic ovaries at risk of ovarian hyperstimulation syndrome, as well as in other indications such as for immediate aspiration of oocytes prior to gonadotoxic treatment in cancer patients. Compared with in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI), IVM is not associated with increased risk of multiple pregnancy, cesarean delivery, and congenital abnormality.
Besides transvaginal aspiration of small ovarian follicles, immature oocytes can be aspirated directly from removed ovarian tissue prior to its cryopreservation. In addition, the aspiration of immature oocytes during various gynecologic procedures, including cesarean section (CS), has become increasingly relevant with the introduction of IVM as a standard procedure in many IVF centers worldwide. This has been accompanied by an ongoing search for new options for fertility preservation. The aim of this work is to report a case of oocyte aspiration during CS for fertility preservation and future surrogacy.
Case Report
A 38-year-old pregnant patient with a history of renal transplantation sought embryo freezing for fertility preservation and future surrogacy. A CS and tubal ligation were scheduled on the 37th week of gestation. The procedure was approved by the local institutional review board. Under spinal block, direct aspiration of small ovarian follicles (2-5 mm) was performed using a simple 2-mL syringe and a 21-gauge needle. The procedure was completed within 15 minutes without bleeding or any other postoperative complication. Oocyte-cumulus complexes identified in the aspirated fluid ( Figure ) were cultured in oocyte maturation medium containing 75 mIU of both follicle stimulating hormone and luteinizing hormone in 37°C and denuded 29 hours later. In 5 of the 13 oocytes aspirated a distinct germinal vesicle was observed at retrieval while in the rest the meiotic stage could not be ascertained. On the following day, by the time of enzymatic stripping, 10 oocytes completed their maturation and were inseminated by ICSI. Fertilization was observed in 4 oocytes, which were cryopreserved at the zygote stage. The 3 remaining oocytes underwent germinal vesicle breakdown but failed to extrude the first polar body.
Comment
This case shows that aspirating competent oocytes during CS can be an additional fertility preservation procedure when the need arises during pregnancy. Furthermore, this procedure may also be routinely offered for IVF pregnant patients who are scheduled for elective CS, thus preventing the need for a subsequent fresh IVF cycle.
Direct aspiration of immature oocytes during CS was previously reported by several investigators in animals and in human beings; in a baboon model at the time of CS, Brzyski et al aspirated a total of 246 oocytes (mean, 35; range, 14–67). A total of 87 oocytes (35%) underwent germinal vesicle breakdown and 72 oocytes (29%) extruded a polar body. No effect of gestational age or maternal age on oocyte yield or development was observed. In the first human report, Cha et al aspirated 270 immature oocytes from 23 ovaries removed for various gynecologic indications. The maturation rates in mature follicular fluid or fetal cord serum were 55.8% and 35.9%, respectively. In the oocyte donation program, 5 embryos were transferred and she subsequently delivered healthy triplet girls. The authors suggested that IVM of immature oocytes from unstimulated ovaries could be used successfully in a donor oocyte program after IVF. Hwang et al also reported a similar case of pregnancy in an oocyte donation program when 2 of 7 immature oocytes, aspirated during CS, became metaphase II oocytes, and both were fertilized by ICSI. In a later randomized study, the same group of investigators compared the fertilization rate of oocytes that were aspirated during CS using standard IVF insemination or ICSI. They concluded that cumulus cells are beneficial in the IVM of the oocytes and that ICSI increases the fertilization rate for the in vitro matured oocytes. However, the developmental potential of the fertilized oocytes was similar, irrespective of the fertilization method or the presence or absence of cumulus cells.
In the largest reported study, Hwu et al investigated whether the developmental competence of human embryos following IVM/IVF from nonstimulated follicles could be enhanced by the use of a human ampullary cell coculture system. A total of 268 immature oocytes were aspirated from small follicles of 51 patients at the time of CS at 37-41 weeks of gestation (1-15 oocytes; mean, 5.3). Of 48 embryos cultured in conventional medium alone, all arrested at the 2- to 16-cell stage on day 3 after insemination. Of the 46 embryos cultured in the coculture system, 6 embryos (13%) developed to the morula stage and 14 embryos (30.4%) developed to expanded blastocysts. In their discussion the authors wrote that “…in the future, the use of immature oocytes from Caesarean sections may not only contribute to the oocyte donation programme, but may also be used for pregnant women using IVF procedures who desire another pregnancy but who do not have spare frozen embryos.”
In a unique report, Demirtas et al presented 3 women seeking fertility preservation prior to chemotherapy who underwent immature oocyte retrieval in the luteal phase and 7, 5, and 7 immature oocytes were recovered, respectively. After IVM, 5, 3, and 5 matured oocytes were vitrified. As the luteal phase resembles, at least in part, the high progesterone levels similar to the pregnant state, it seems that the unique hormonal milieu to which the follicles are exposed during the luteal phase and pregnancy does not hamper the developmental capacity of the oocyte.
In conclusion, aspiration of small follicles during CS offers an additional fertility preservation procedure during pregnancy. This procedure may also be offered for IVF pregnant patients who are scheduled for elective CS, thus preventing the need for a subsequent fresh IVF cycle. In our view, the use of this technique in oocyte donation program remains controversial and should be avoided.
Reprints not available from the authors.