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. 2016 Jan;214(1):94.e1-9.
doi: 10.1016/j.ajog.2015.10.001. Epub 2015 Nov 18.

First Pregnancies, Live Birth, and in Vitro Fertilization Outcomes After Transplantation of Frozen-Banked Ovarian Tissue With a Human Extracellular Matrix Scaffold Using Robot-Assisted Minimally Invasive Surgery

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Free PMC article

First Pregnancies, Live Birth, and in Vitro Fertilization Outcomes After Transplantation of Frozen-Banked Ovarian Tissue With a Human Extracellular Matrix Scaffold Using Robot-Assisted Minimally Invasive Surgery

Kutluk Oktay et al. Am J Obstet Gynecol. .
Free PMC article

Abstract

Background: Ovarian tissue cryopreservation is an experimental fertility preservation method and the transplantation techniques are still evolving.

Objective: We attempted to improve the technique with the utility of a human decellularized extracellular tissue matrix (ECTM) scaffold, robot-assisted minimally invasive surgery, and perioperative pharmacological support.

Study design: We prospectively studied 2 subjects with hemophagocytic lymphohistiocytosis (patient A) and non-Hodgkin lymphoma (patient B) who underwent ovarian tissue cryopreservation at the age of 23 years, before receiving preconditioning chemotherapy for hematopoietic stem cell transplantation. Both experienced ovarian failure postchemotherapy and we transplanted ovarian cortical tissues to the contralateral menopausal ovary 7 and 12 years later, using a human ECTM scaffold and robotic assistance. The ECTM scaffold tissue compatibility was shown in preclinical studies. Patients also received estrogen supplementation and baby aspirin preoperatively to aid in the revascularization process.

Results: Ovarian follicle development was observed approximately 10 (patient A) and 8 (patient B) weeks after ovarian tissue transplantation. Following 8 and 7 cycles of in vitro fertilization, 9 and 10 day-3 embryos were cryopreserved (patients A and B, respectively). While the baseline follicle-stimulating hormone (range 3.6-15.4 mIU/mL) levels near normalized by 7 months and remained steady postovarian transplantation in patient A, patient B showed improved but elevated follicle-stimulating hormone levels throughout (range 21-31 mIU/mL). Highest follicle yield was achieved 14 (8 follicles; patient A) and 11 (6 follicles; patient B) months postintervention. Patient A experienced a chemical pregnancy after the third frozen embryo transfer attempt. She then conceived following her first fresh in vitro fertilization embryo transfer and the pregnancy is currently ongoing. Patient B conceived after the first frozen embryo transfer attempt and delivered a healthy girl at term.

Conclusion: We report the first pregnancies after the minimally invasive transplantation of previously cryopreserved ovarian tissue with an ECTM scaffold. This approach seems to be associated with steady ovarian function after a follow-up of up to 2 years.

Keywords: AlloDerm; fertility preservation; in vitro fertilization; ovarian cryopreservation and transplantation; robotic surgery; translational research.

Conflict of interest statement

The authors report no conflict of interest.

Figures

Fig 1
Fig 1
Preoperative evaluation of extracellular matrix (ECTM) scaffold. A. Medium thickness ECTM during rehydration. B. Xenografting of ECTM (white arrows) with ovarian tissue (black arrows) to severe combined immunodeficiency (SCID) mouse. C. Gross, and D. histological evaluation showing proper integration of ECTM (white arrow) into ovarian tissue (black arrow).The transition zone begins where the tails of the two arrows oppose. Note the presence of normal appearing primordial follicles (arrowheads) near the transition zone.
Fig 2
Fig 2
Timeline from freezing to post-ovarian transplant. (A) Patient A. (B) Patient B. w: weeks; p-OTT: post-ovarian tissue transplant; OTT: ovarian tissue transplant; E2: estradiol; FSH: follicle stimulating hormone; LH: luteinizing hormone; AMH: antimüllerian hormone; P4 : progesterone; C. luteum: corpus luteum; US: ultrasound; OCP: oral contraceptive pill; HRT: hormone replacement therapy; ASA: acetylsalicylic acid; IVF: in vitro fertilization; E: endometrial thickness.
Fig 3
Fig 3
Ovarian transplantation outcomes. (A). Robust response to ovarian stimulation in P-A, 14 months after the ovarian tissue transplant (OTT). (B). Nine embryos were frozen from P-A after 8 IVF cycles; embryo grades are indicated adjacent to each embryo. (C). In addition, 2 embryos were transferred fresh in the last IVF cycle, which resulted in an ongoing pregnancy. (D-E). Respective early follicular phase FSH, LH and estradiol levels in P-A and P-B, indicating improvement in ovarian function after the OTT. (F). Multiple follicle development 11-months post-OTT in P-B. (G). Transplanted ovary at second-look laparoscopy. (H). Eight embryos were frozen from P-B after 7 IVF cycles; embryo grades are indicated adjacent to each embryo. (I). A 20-week fetal anatomical scan shows a normally developed fetus in P-B.

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