Delivery of a Healthy Child Through International Gestational Surrogacy 10 Years Following Female Fertility Preservation and In Vitro Fertilization (IVF) for Recurrent Breast Cancer: A Case Report

Assisted reproduction technology (ART) has made considerable progress in recent years; in particular with regard to cryopreservation, long-term storage, successful thawing, and embryo transfer of cryopreserved embryos. Regarding gestational surrogacy, progress has been made in the areas of awareness, social acceptance, regulation, legislation, availability, streamlining, and optimization of cross-border care. The above is being highlighted in the current presentation of a particularly challenging and novel case. A 43-year-old woman visited our clinic in Greece, seeking international gestational surrogacy due to recurrent breast cancer which rendered her medically unfit for pregnancy. Ten years before her initial visit to our clinic the patient had undergone fertility preservation due to breast cancer, her oocytes had been fertilized with her husband’s sperm, and the embryos were cryopreserved and stored in a fertility clinic based in the United Kingdom. The stored embryos were transported to Greece, thawed, and successfully implanted to the selected gestational surrogate. Following an uneventful pregnancy, the surrogate delivered a healthy girl. This successful outcome exemplified innovation, motivation, and hope and may represent a paradigm of team scientific excellence associated with positive patient outcomes. Furthermore, this case constitutes the successful culmination of major advances made in various different sectors of cross-border reproductive care; laboratory, clinical, legal, ethical, and logistical.


Introduction
Infertility is becoming an increasingly prevalent issue in the modern world, with increasingly more couples seeking Assisted Reproduction Technology (ART) services [1]. Given the diverse causes of infertility and the potential contribution of both partners to it, a plethora of ART services are available, tailored to the needs of each individual case. Fertility preservation is one such service, which may be applied prior to surgical or medical treatment that may adversely affect the fertility potential of women and men. This process entails the extraction, cryopreservation and storage of genetic material or embryos and its use at a later time, when it is medically safe and indicated or based on the couple's family programming, with long term cryo-storage of embryos not being an uncommon occurrence.
However, in certain challenging cases, even if fertility preservation has been performed, pregnancy and delivery may not be medically indicated or feasible, due to anatomical, metabolic, iatrogenic or other reasons. For these cases, another ART technique, gestational surrogacy (GS) may be indicated and available, as an advanced, final-line fertility treatment. Entailing the implantation and gestation of an embryo created from the genetic material of the intended parents to the uterus of a surrogate mother, GS is a challenging, but rewarding and effective programme and sometimes the only option available to certain individuals to become parents.
The aforementioned ART techniques may be further complicated in cases of cross-border patients and when genetic material is required to be transported between different countries. Under these circumstances, legal and logistical considerations further exacerbate the already difficult journey of the patients [2]. Despite all these challenges, the constant evolution of ART services, equipment, protocols, legislation and logistics have led to remarkable progress in modern fertility care and improved patient outcomes.
The aim of this report is to highlight this remarkable progress through the presentation of a case of successful delivery of a healthy child through cross-border GS with the use of cryopreserved embryos stored for over a decade abroad, following fertility preservation for breast cancer. Open Access Case Report DOI: 10.7759/cureus.

Case Presentation
The current report presents the case of a 43 year old woman and her 48 year old husband who became parents via an international gestational surrogacy programme. The couple first contacted our Clinic regarding this matter in 2019. The woman had been diagnosed with breast cancer in 2010, which was treated surgically and with adjuvant chemotherapy, hormonal therapy and radiotherapy. Prior to her breast cancer treatment, the patient had undergone fertility preservation in the UK at age 34 years.
Following ovarian stimulation, oocyte retrieval, IVF and ICSI, five embryos were created. The embryos were cultured using the SAGETM sequential medium, until they reached the fifth day of development, with one reaching the sixth day (blastocyst stage). Subsequently, the embryos were cryopreserved via the slow-freeze method, using the Quinn's AdvantageTM blastocyst freeze kit (Ref. No: ART-8015). The embryos were stored in PETGTM 91mm embryo straws (Ref. No: 006433) and remained in storage at a fertility clinic in the UK.
The patient continued her breast cancer treatment with Tamoxiphen for five years post-operatively and underwent frequent follow-up examinations. Two years following the end of her hormonal treatment, the patient initiated pre-ART investigations in the UK with a view to proceed with frozen/thawed embryo transfer. However, three years after the end of her hormonal treatment, (8 years following the initial breast cancer diagnosis and treatment), the patient suffered from breast cancer recurrence and she underwent bilateral mastectomy and bilateral axillary lymphadenectomy. Histopathological analysis revealed a G2 invasive ductal adenocarcinoma in the left breast, 17mm in diameter, without lymph-node metastases, ERpositive and HER2-negative. Postoperatively, the patient was treated with Letrozole and Goserelin.
Given the patient's medical history, IVF and pregnancy were contraindicated and gestational surrogacy was offered as a fertility option. Due to availability issues in the UK, the couple opted for international gestational surrogacy care in our Clinic in Greece. The cryopreserved embryos were subsequently transported to our Clinic, with the use of a specialized courier service, certified for cross-border transport of human genetic material. Following screening and medical, logistics, and preparation including an individualized court order, the gestational surrogate underwent an embryo transfer attempt in late 2020.
One of the received embryos, cryopreserved for 10 years at that point, was thawed, using the FertiProTM Warming Kit (Lot No: FP20FVW10) and cultured for 4 hours in a continuous single culture, supplemented with human serum albumin. This first embryo however did not survive the thawing process, therefore, two more were thawed using the same protocol and, following laser-assisted hatching (LAH), were transferred to the gestational surrogate. Embryo transfer was performed with the use of a Wallace….., under uss guidance….
The transferred blastocysts were of 3BB and 3AB quality according to the Gardner score scale [3] (Figure 1). This embryo transfer resulted in pregnancy loss at 6 weeks of gestation. A second embryo transfer with the same gestational surrogate was performed in early 2021. A single embryo was thawed using the the FertiProTM Warming Kit (Lot No: FP20FVW10), cultured for 3 hours and 30 minutes in a continuous culture supplemented with 20% human serum albumin and transferred, with the transferred blastocyst being of 2AA quality ( Figure 2). Embryo characteristics, embryo transfer parameters and outcomes are summarized on Table 1.
This second embryo transfer was successful, resulting in a healthy singleton and uneventful pregnancy, which resulted in a spontaneous vaginal delivery of a healthy girl at 36 weeks and 3 days gestation. The neonate weighed 2620 g, had normal APGAR scores and required no specialized interventions and intensive care. At present, the child has demonstrated normal physical and cognitive development, with no abnormalities whatsoever.