DOI: 10.2478/pielxxiw-2021-0010 © 2021 Uniwersytet Medyczny w Lublinie. This is an open access article distributed under the Creative Commons Attribution-NonComercial-No Derivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) Motherhood of women with uterine factor infertility Macierzyństwo kobiet z macicznym czynnikiem niepłodności Agnieszka Bień1 , Agnieszka Pieczykolan2 , Joanna Grzesik-Gąsior2 , Artur Wdowiak3 , Marcin Czop4 , Grażyna Iwanowicz-Palus1 1Faculty of Health Sciences, Medical University of Lublin, Poland 2Student, Faculty of Health Sciences, Medical University of Lublin, Poland 3Diagnostic Techniques Unit, Medical University of Lublin, Poland 4Department of Clinical Genetics, Medical University in Lublin, Lublin, Poland CORRESPONDING AUTHOR: Agnieszka Pieczykolan Faculty of Health Sciences, Medical University of Lublin, Poland Staszica 4/6, 20-081 Lublin e-mail: [email protected] STRESZCZENIE MACIERZYŃSTWO KOBIET Z MACICZNYM CZYNNIKIEM NIEPŁODNOŚCI Cel pracy. Celem pracy jest przedstawienie alternatywnych możliwości macierzyństwa kobiet z macicznym czynnikiem niepłodności. Materiał i metody. Analiza fachowej literatury obejmującej problematykę macierzyństwa zastępczego, przeszczepu macicy oraz ektogenezy. Wyniki. Niepłodność spowodowana czynnikiem macicznym dotyczy 3-5% kobiet na świecie. Istnieje grupa kobiet, które pomimo nieprawidłowej budowy macicy lub jej braku chcą posiadać dziecko z własnego materiału genetycznego. Medycyna, starając się wyjść naprzeciw potrzebom części społeczeństwa, umożliwia im zapłodnienie pozaustrojowe i wszczepienia zarodka do jamy macicy innej kobiety (macierzyństwo zastępcze), bądź – w szczególnych przypadkach – można dokonać u takiej pacjentki przeszczepu macicy w celu zajścia w ciążę. Inną kontrowersyjną ideą jest ektogeneza, czyli technologia, która pozwoliłaby na rozwój ludzkich embrionów poza organizmem kobiety, w sztucznej macicy. Opcja surogacji jest brana pod uwagę, gdy leczenie i inne metody rozrodu nie przyniosły zamierzonych efektów. Procedura ta w niektórych państwach jest legalna i akceptowana, w innych, natomiast spotyka się ze stanowczym sprzeciwem. Podsumowanie. Wzrasta zapotrzebowanie na stosowanie odpowiednich i nowoczesnych metod diagnostycznych i leczniczych umożliwiających reprodukcję. Proponowane rozwiązania mogą wydawać się wręcz nierzeczywiste, jednak wyniki prowadzonych badań naukowych mających na celu ich ucieleśnienie wydają się być obiecujące. Słowa kluczowe: niepłodność, macica, surogacja, przeszczep macicy, ektogeneza ABSTRACT MOTHERHOOD OF WOMEN WITH UTERINE FACTOR INFERTILITY Aim. The aim of this paper is to present alternative ways for women with uterine factor infertility to achieve motherhood. Material and methods. Analysis of professional literature including the issues of surrogate motherhood, uterine transplantation and ectogenesis. Results. The infertility caused by uterine factor aff ects 3-5% of women in the world. There are also women who wish to conceive a baby out of their own genetic material, despite having a structurally abnormal uterus or lacking this organ altogether. Due to considerable advancements in reproductive medicine, the needs of such women can now be met via extracorporeal fertilisation and embryo implantation into the uterine cavity of another woman – surrogacy, or in special cases, via uterus transplantation. Another controversial concept is ectogenesis, i.e. technology which would allow for the growth of human embryos outside the mother’s body in an artifi cial uterus. The surrogate is considered when treatment and other reproduction methods have not worked well. This procedure is legal and accepted in some countries, while in others it is strongly opposed. Summary. There is growing demand for accurate and modern diagnostic and therapeutic methods allowing for successful reproduction. The proposed solutions may seem unreal, but the results of the research carried out to embody them seem to be promising. Key words: infertility, uterus, surrogacy, uterus transplantation, ectogenesis 23 Motherhood of women with uterine factor infertility INTRODUCTION malformations or obstruction of the cervical canal. Normal anatomical structures in the uterine cavity may Infertility is diagnosed in an ever-increasing number of also be damaged due to numerous factors leading to the men and women, denying them the possibility of having obliteration of the uterine cavity (called Asherman’s syn- their own offspring. This makes reproductive failure drome). Intrauterine adhesions may be a complication of a medical, social and demographic problem affecting surgical procedures in the uterine cavity, such as excessive nearly 20% of couples of reproductive age in Europe [1]. D&C (dilation and curettage) during delivery or abor- The etiopathogenesis of infertility may be related to gene- tion, or following a C-section. Asherman’s syndrome may tic and epigenetic abnormalities, concomitant systemic be induced by endometrial ablation (surgical removal and contagious diseases, lifestyle, and environmental or of the endometrium used to treat excessive uterine ble- occupational factors [2]. eding), endometrial infection (e.g. genital tuberculosis), Due to the considerable decrease in fertility, the only and less frequently by schistosomiasis (a disease caused chance for some couples to have their own children is by blood parasites) or severe endometritis [10,11]. Ute- in vitro fertilisation (IVF). In 1978, the world’s first IVF rine deformity may also be caused by fibroids which may baby, Louise Brown, was born in the UK. Since then, the lead to embryo implantation failure, miscarriage, or pla- method has been widely used for selected medical indi- cental abruption, making pregnancy impossible in some cations [3]. Advances in medicine have brought improve- cases. Risk factors for uterine fibroids include age, African ments in the IVF process and embryo transfer. As a result, descent, obesity and no history of pregnancy. Even though the effectiveness of the procedure has increased to 50% in advancements in research have extended the knowledge women aged < 35 years [4]. Indications for the use of the about the pathology of fibroids, their etiology remains to method include fallopian tube obstruction, severe endo- be fully understood [12]. Structural abnormalities of the metriosis or severe male factor. The IVF method is also uterus may also stem from congenital uterine anomalies, useful in cases of structural uterine abnormalities, with uterine agenesis or hysterectomy (e.g. due to postpartum the embryo being transferred to the uterus of a surrogate uterine atony) [6,12,13]. Congenital structural anoma- mother. The development of the IVF technique created the lies of the uterus constitute frequent malformations of need for testing whether the embryo presents any genetic the female reproductive system. Their actual prevalence abnormalities. Pre-implantation testing used for this pur- is not known, but it is estimated to be about 3-5% in the pose includes pre-implantation genetic screening (PGS) general population. The etiology of these malformations and pre-implantation genetic diagnosis (PGD): qPCR, remains unknown. However, their development may be comparative genomic hybridization (CGH), SNP array, influenced by genetic makeup, adverse environmental and array comparative genomic hybridization (aCGH), fluore- mechanical factors, and also pharmacological agents [6,7]. scence in situ hybridization (FISH), DNA sequencing, and Uterine anomalies are mostly sporadic, but there are also whole-genome amplification (WGA) [5]. A significant role familial cases which have proven that the defects can be in the etiopathogenesis of reproductive disorders is played inherited. There are a number of genes whose mutations by the female infertility factor. Absolute infertility caused lead to uterine defects, i.e. uterine aplasia, unicornuate by uterine factors affects 3-5% of women worldwide [6,7]. uterus – the LHX1, WNT4, WNT5A, WNT7A, WNT9B, There are women who wish to conceive a baby out of their and TBX6 genes; bicornuate uterus – the LHX1, WNT9B, own genetic material, despite having a structurally abnormal EMX2, HOXA9, HOXA10, PAX2, and TBX6 genes; septa- uterus or lacking this organ altogether. To meet their needs, ted uterus – the HNF1B, HOXA10, HOXA11, and TBX6 reproductive medicine offers in vitro fertilisation and embryo genes [14]. The Mayer–Rokitansky–Küster–Hauser syn- implantation into the uterine cavity of another woman – sur- drome (MRKH), on the other hand, usually develops in rogacy, or in special cases – uterus transplantation [8,9]. The women with a normal karyotype (46,XX). However, it is aim of this paper is to present alternative ways for women believed that genetic factors play a role in its etiology. Of with uterine factor infertility to achieve motherhood. all genes, only WNT4 has been proven to be involved in the etiopathogenesis of MRKH. Other possible causative AIM genes include: GALT, CFTR, MIF, MHR, LHX1, HNF1B, and TBX6 [15,16]. The aim of this paper is to present alternative ways for women with uterine factor infertility to achieve motherhood. Surrogacy Surrogacy is taken into account when treatment and MATERIALS AND METHODS other reproductive methods have not delivered the expec- ted results. Medical indications for surrogacy include: ute- Analysis of professional literature including the issues rine factors in infertility; uterine defects caused by surgical of surrogate motherhood, uterine transplantation and intervention