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First Live Birth After Uterus Transplantation in the Middle East

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First Live Birth After Uterus Transplantation in the Middle East Akouri et al. Middle East Fertility Society Journal (2020) 25:30 Middle East Fertility https://doi.org/10.1186/s43043-020-00041-4 Society Journal RESEARCH Open Access First live birth after uterus transplantation in the Middle East Randa Akouri1* , Ghassan Maalouf2, Joseph Abboud2, Toufic Nakad2, Farid Bedran2, Pascal Hajj2, Chadia Beaini2, Laura Mihaela Cricu3, Georges Aftimos4, Chebly El Hajj2, Ghada Eid2, Abdo Waked2, Rabih Hallit2, Christian Gerges2, Eliane Abi Rached2, Matta Matta2, Mirvat El Khoury2, Angelique Barakat2, Niclas Kvarnström5, Pernilla Dahm-Kähler1 and Mats Brännström1,6 Abstract Background: The first live birth after uterus transplantation took place in Sweden in 2014. It was the first ever cure for absolute uterine factor infertility. We report the surgery, assisted reproduction, and pregnancy behind the first live birth after uterus transplantation in the Middle East, North Africa, and Turkey (MENAT) region. A 24-year old woman with congenital absence of the uterus underwent transplantation of the uterus donated by her 50-year-old multiparous mother. In vitro fertilization was performed to cryopreserve embryos. Both graft retrieval and transplantation were performed by laparotomy. Donor surgery included isolation of the uterus, together with major uterine arteries and veins on segments of the internal iliac vessels bilaterally, the round ligaments, and the sacrouterine ligaments, as well as with bladder peritoneum. Recipient surgery included preparation of the vaginal vault, end-to-side anastomosis to the external iliac arteries and veins on each side, and then fixation of the uterus. Results: One in vitro fertilization cycle prior to transplantation resulted in 11 cryopreserved embryos. Surgical time of the donor was 608 min, and blood loss was 900 mL. Cold ischemia time was 85 min. Recipient surgical time was 363 min, and blood loss was 700 mL. Anastomosis time was 105 min. Hospital stay was 7 days for both patients. Ten months after the transplantation, one previously cryopreserved blastocyst was transferred which resulted in viable pregnancy, which proceeded normally (except for one episode of minor vaginal bleeding in the 1st trimester) until cesarean section at 35 + 1 weeks due to premature contractions and shortened cervix. A healthy girl (Apgar 9-10- 10) weighing 2620 g was born in January 2020, and her development has been normal during the first 6 months. Conclusions: This is the first report of a healthy live birth after uterus transplantation in the MENAT region. We hope that this will motivate further progress and additional clinical trials in this area in the Middle East Region, where the first uterus transplantation attempt ever, however unsuccessful, was performed already three decades ago. Keywords: Human, Infertility, Transplantation, Uterus, Middle East * Correspondence: [email protected] 1Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-41345 Göteborg, Sweden Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Akouri et al. Middle East Fertility Society Journal (2020) 25:30 Page 2 of 7 Background The 50-year-old donating mother (blood group A+; Research on uterus transplantation (UTx) dates back to BMI 32 kg/m2) had six normal pregnancies and vaginal the 1960s and was mostly conducted in dogs. The goal births. Her last menstruation was 4 months before donor was to establish an animal model of en bloc utero-tubal- hysterectomy. She had no history of miscarriage or ovarian transplantation to further allow the treatment of extra-uterine pregnancy. She smoked water-pipe sporad- tubal factor infertility [1]. Due to the lack of effective ically and was not on any medications. immunosuppression, and later success of IVF, these projects were abandoned, since IVF became a highly Pre-operative investigations on donor and recipient successful treatment option for women with tubal factor Both recipient and donor underwent extensive medical infertility [2, 3]. However the group of women with ab- and psychological investigations including imaging, ser- solute uterine factor infertility (AUFI), due to congenital/ ology, clinical chemistry, HLA typing, and crossmatching surgical absence of a uterus or presence of a non-functional as well as psychological evaluation as described previously uterus, remained without any treatment options [4]. [14]. Gynecological examination included evaluation of The Swedish team at the Sahlgrenska Academy, Univer- the vagina and cervix (donor) and sampling for chlamydia, sity of Gothenburg, was established in 1998 and during gonorrhea, and high-risk human papilloma virus (HPV). more than 10 years preclinical research on several animal Transvaginal ultrasound (TVU) was performed in both models, including syngeneic UTx in mice, allogeneic UTx recipient and donor. The vascularity of the uterus was in rats, autologous UTx in sheeps, and allogeneic UTx in studied by a combination of contrast-enhanced MRI and non-human primates, was conducted [5–12]. Later on, the conventional digital subtraction angiography with selective Swedish team started the first clinical trial on UTx and contrast into internal iliac arteries, through a femoral that was a living donor trial initiated in 2012 [13]. It re- artery catheter. sulted in the first ever live birth after UTx in 2014 [14]. The recipient underwent MRI of the pelvis and abdomen, Thereafter, a restricted number of live births have been with a special focus on vascular anatomy and kidney/ureter reported both after live donor and deceased donor UTx positions. trials, albeit with no successful UTx procedure reported from the Middle East region [15–17]. Since then, a second In vitro fertilization Swedish trial, including robotically assisted donor surgery One in vitro fertilization (IVF) cycle to cryopreserve em- has been performed with births achieved [18, 19]. bryos was performed 4 months prior to UTx. The male The first two UTx attempts took place in the Middle partner (aged 30) had a normal semen sample. Ovarian East, North Africa, and Turkey (MENAT) region. In stimulation started 5 days after the last combined oral 2000, a group of Saudi doctors attempted an unrelated contraceptive pill (COCP) by daily administration of living donor UTx, but 99 days after the surgery, hyster- 300 IU of recombinant follicle-stimulating hormone ectomy was required due to thrombosis in uterine blood (FSH) s.c. and cetrorelix acetate 0.25 mg s.c. from day 6 vessels [20]. In 2011, a Turkish team performed the of stimulation (fixed antagonist protocol). Ovulation was second UTx attempt in the MENAT region by a deceased triggered with gonadotropin-releasing hormone (GnRH) donor UTx procedure. Early miscarriages were initially agonist triptorelin 0.2 mg s.c. and urinary human chori- reported, but no live birth (end-point and definition of onic gonadotropin (hCG) 1500 IU. Cryopreservation was success of UTx) has been reported so far [21]. by vitrification. We present the first live birth after UTx in the MENA T region, which was a result of Swedish-Lebanese- Surgery—donor Jordanian cooperation. The surgical procedures of donor, recipient, and anesthesia have previously been described in details [13]. Donor surgery entailed isolation of the uterus (exclud- Methods ing oviducts) together with major arteries (uterine and Recipient and donor anterior internal iliac branches) and major uterine veins The 24-year-old recipient (blood group AB+; BMI 26 kg/ bilaterally and efficaciously without complications. The m2) had uterine agenesis as part of Mayer-Rokitansky- ovarian vein was obliterated on the left side with atro- Küster-Hauser (MRKH) syndrome. She had bilateral phic ovary. The graft included parts of the internal iliac kidneys at typical positions corresponding with MRKH veins and arteries as previously described. Substantial syndrome type 1. Initially, she attempted vaginal lengthen- parts of the round ligaments and the sacrouterine ing by intercourse obtaining 4 cm vaginal length and then ligaments, as well as an extensive sheet of the bladder used dilator for 4 months before surgery, obtaining 8-cm peritoneum, were preserved on the graft side to enable long vagina. The recipient was not on any medication. She stable fixation of the uterus in the recipient. The major smokes water-pipe sporadically. feeding arteries and veins were then clamped and severed, Akouri et al. Middle East Fertility Society Journal (2020) 25:30 Page 3 of 7 before the uterus was removed from the pelvis to a back- Post-operative follow-up table setting. Clamping points of the donor’s internal iliac Gynecological examinations were performed
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