Milan Milenkovic

Livebirth after uterus transplantation

BACKGROUND Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. METHODS In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. FINDINGS The recipient and the donor had essentially uneventful postoperative recoveries. The recipients first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. INTERPRETATION We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. FUNDING Jane and Dan Olsson Foundation for Science.

Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide

PurposeTo evaluate a slow freezing method for whole ovary cryopreservation by evaluating effects of added cryoprotectant.MethodsSheep ovaries were isolated during surgery, flushed with either Ringer-Acetate or dimethylsulphoxide and cryopreserved by slow freezing. After rapid thawing, viability was assessed by ovarian in vitro perfusion, cell culture, histology and fluorescent live-dead assay.ResultsProduction of cyclic AMP and progesterone was slightly higher in the dimethylsulphoxide group. Cultured ovarian cells from dimethylsulphoxide-preserved ovaries secreted larger amounts of progesterone than cells from Ringer-Acetate preserved. Light microscopy of ovarian biopsies obtained after perfusion, revealed well-preserved tissue in the dimethysulphoxide group but not in the Ringer-Acetate group. The density of small follicles and ovarian cell viability were higher in dimethysulphoxide ovaries compared to Ringer-Acetate ovaries.ConclusionsEquilibrium with its protective effect can be achieved by slow freezing protocol, with an additional protective effect by the presence of dimethylsulphoxide.

Advances in fertility preservation for female cancer survivors

A method using tissue engineering principles for the culture of immature ovarian follicles followed by fertilization of oocytes in vitro has been presented by Xu et al.. This methodology is a great step forward toward new technology for fertility preservation in female cancer patients.

Live birth after uterus transplantation

ABSTRACTIn the 3 decades since the birth of the first in vitro fertilization baby in 1978, there have been remarkable advances in infertility treatment. Until now, however, absolute uterine factor infertility remained the only major type of female infertility viewed as untreatable. Absolute uterine

Spontaneous twin pregnancy with live births after cryopreservation and re-implantation of ovarian tissue

Methods A 27-year-old, 1-parous patient suffered from Hodgkin’s lymphoma in 2011. Pre-operative transvaginal sonography (TVS) revealed a normal uterus, the left side ovary with a unilocular cyst of 50 × 70 mm and the right ovary with 8 antral follicles. Laparoscopic stripping of left ovarian cyst and right-sided oophorectomy was performed with subsequent standard OTC of 15 cortical strips [5] before six chemotherapy treatments with BEACOPP (bleomicin, etoposide, adryamicin, cyclophosphamide, oncovin, procarbazine, prednisolone). Histology showed benign mucinous cystadenoma. After chemotherapy, patient experienced amenorrhea and climacteric symptoms that were treated by hormonal replacement therapy (HRT). HRT was ceased in October 2013 due to benign cysts in the breast, and the patient developed oligomenorrhea. Hormonal status after chemotherapy is presented in Fig. 1a. Patient was considered free of disease and tried to conceive for 1 year. In March 2015, TVS showed cyst on the left ovary and laparoscopic

The human postmenopausal ovary as a tool for evaluation of cryopreservation protocols towards whole ovary cryopreservation

PurposeCryopreservation of a complete ovary may be a future method for fertility preservation in cancer patients. Difficulties exist in cryopreservation of the relatively large ovarian tissue mass. This study evaluates whether a human postmenopausal ovary can be used, as a complement to animal models, in studies of this research field.MethodsPostmenopausal human ovaries (n = 10) were isolated and flushed through ovarian arteries with either the cryoprotectant dimethylsulphoxide or Ringer-Acetate, followed by slow freezing. After thawing, production of androgens during in vitro perfusion and morphology (light/electron microscopy) were assessed.ResultsThe dimethylsulphoxide-cryopreserved ovaries showed larger secretion of androgens during perfusion than Ringer Acetate-cryopreserved ovaries. Light microscopy showed well preserved morphology in both groups. Electron microscopy revealed normal appearance of stroma and vessels in the dimethylsulphoxide group.ConclusionsThe study demonstrates the potential to use the postmenopausal human ovary for further studies aiming at optimizing cryopreservation protocols, with special reference to ovarian vascularity and stroma.

Review on Ovarian Cryopreservation in Large Animals and Non-Human Primates

The ultimate aim of ovarian cryopreservation research is naturally to increase the effectiveness of this fertility preservation procedure in female cancer victims and much of this research on whole ovary cryopreservation, ovarian cortex cryopreservation and transplantation has been performed in animal models. However, ovarian cryopreservation could also be used in the future in programs with the purpose to rescue endangered species (Santos et al., 2010) and certain specific strains of animals (Dorsch et al., 2004). Due to the ethical barriers in the research on human tissue and the shortage of human premenopausal ovarian tissue for research purposes, there is a need to find animal models that are reasonably analogous to the human. As a general rule, animal models have to be comparable in biochemical, physiological and anatomical characteristics to the human so that the results can be applicable to human conditions (VandeBerg, 2004). Regarding research of ovarian cryopreservation for human fertility preservation, a similar tissue architecture and size of the ovary (Table 1) as well as being a mono-ovulatory species with the primordial follicles located superficially in the cortex would be of advantage (Gerritse et al., 2008). The previous research on ovarian cryopreservation using bovine, porcine, sheep and non-human primate models will be presented in this chapter.