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Controlled ovarian stimulation and cryopreservation of oocytes or embryos

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This is the most established female fertility preservation method. However, it requires approximately 2 weeks to complete the treatment to the oocyte retrieval stage. Ovarian stimulation can be started at any stage of the menstrual cycle, which is called random start protocol (Figure 10.2); however, if it is started in the late follicular phase or luteal phase, it is essential that:

 A follicle stimulating hormone (FSH) only preparation is used, rather than human menopausal gonadotropin (hMG), which contains human chorionic gonadotropin (hCG) driven luteinizing hormone (LH) activity that can induce luteinization); and,Figure 10.2 Controlled ovarian stimulation at various stages in menstrual cycle. FSH, follicle stimulating hormone; GnRH, gonadotropin releasing hormone; HMG, human menopausal gonadotropin.

 A gonadotropin releasing hormone (GnRH) antagonist is started at the same time as the FSH injections (to prevent luteinization if a late follicular phase start, or to induce luteolysis if a luteal phase start).

 GnRH agonist should be used, unless contraindicated, to induce final follicular maturation as it significantly reduces the risk of ovarian hyperstimulation syndrome [10]. GnRH agonist trigger also has an additional value in hormone dependent breast cancer patients as it reduces the estrogen levels in the luteal phase following the trigger with no negative impact on the number of mature oocytes available for storage (see Chapter 51) [11].

For the patients in Case Histories 1 and 2, controlled ovarian stimulation and oocyte retrieval should be offered, as long as approximately 2 weeks delay in cancer therapy is acceptable. For the woman in Case History 1, cryopreservation of oocytes and/or embryos should be offered. However, with embryos there could always be a risk that she would not be able to use them if her partner withdraws consent to the use of embryos (see Chapter 108). One way of addressing this risk is to divide the lot of oocytes in half, and store half as embryos and the other half as oocytes; alternatively, the woman may decide to cryopreserve oocytes, rather than create any embryos with her partner’s sperm. Two additional issues are worth considering for the woman in Case History 1:

1 As she has an estrogen receptor positive breast cancer, the co‐administration of 5 mg of letrozole daily, commencing on Day 2 and continued throughout COS, is recommended as it reduces peak estradiol concentrations without significantly decreasing oocyte yield (see Chapter 51) [12].

2 As a pregnancy will be associated with very high levels of estrogen, gestational surrogacy may need to be considered [13].

For the girl in Case History 2, oocyte cryopreservation should be offered. The success rate of oocyte cryopreservation has risen, and the increasing use of vitrification has improved outcomes, with IVF pregnancy rates now similar to those achieved with fresh oocytes [14]. There is no evidence that babies born from cryopreserved eggs have an increased risk of congenital abnormalities [15].

Assisted Reproduction Techniques

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