{"paper_id":"79c4a62e-90e7-4a52-80b6-5cfe0f467b26","body_text":"Submit Manuscript | http://medcraveonline.com\nAbbreviations: POI, premature ovarian insufficiency; PROM, \npremature rupture of membranes; MSCs, mesenchymal stem cells; \nAMH, anti-Müllerian hormone; BTO, bilateral tubal obstruction; FSH, \nfollicle stimulating hormone; LH, luteinizing hormone; WG, weeks \nof gestation; COS, controlled ovarian stimulation; RDE, retained \ndead egg; NK, natural killers; TNF-α, tumor necrosis factor alpha; \nlymphotoxin-alpha; AD-MSCs, adipose tissue derived mesenchymal \nstem cells; UC-MSCs, umbilical cord-mesenchymal stem cells; BCU, \nbank of umbilical cord of México\nBackground\nIn Mexico, 17% of women of childbearing age have infertility \nproblems, which is equivalent to 1.4 million of couples requiring \nassisted reproduction techniques, 1,2 from which, 9 to 25% of the \npatients may show a low ovarian response defined as a poor obtention \nof oocytes after an ovarian stimulation. 3,4 This alteration may be \nassociated to Premature Ovarian Insufficiency (POI) characterized by \nan increase of the Follicle Stimulating Hormone (FSH), and Luteinizing \nHormone (LH), with diminution of Anti-Müllerian Hormone (AMH), \nand estrogens, including menstrual modifications before 40 years old \n(oligomenorrhea or amenorrhea),5–7 with a prevalence of 1 out of 100 \nwomen before 40, and 1 out of 1000 women before 30. The risk varies \ndepending on the race, from 0.1% in Japanese to 1% in Caucasians, \nand 1.4% in Africans and Hispanics.7–9 Diverse POI etiopathogeneses \nhave been described; i.e. autoimmune diseases, 10 oxidative stress, 11 \ngenetic predisposition, 12 radiotherapy, and chemotherapy in the \ntreatment of cancer.13–15 This can lead to problems of collection and \nmaintenance of primordial follicles, in addition to the induction of \nfollicular atresia, and apoptosis of granulosa cells.16–19 Only 5 to 15% \nof these patients are able to have a spontaneous pregnancy.20–22 \nOn the other hand, Premature Rupture of Membranes (PROM) is \ndefined as the rupture of ovular membranes before labor begins. They \nare classified as \n1) Term: after 37 Weeks of Gestation (WG)\n2) Preterm: before 37 WG\n3) Prolonged: more than 24 hours of rupture (it may be combined \nwith the previous two) \n4) Previable: occurs before 24 WG. \nThe pathogenesis of PROM is uncertain, but it is thought that is \ncaused by a physiological weakening of membranes due to a decrease \nin the resistance. It is a complication in 3% of pregnancies and causes \na 25-30% of preterm deliveries; therefore, it is considered as the main \ncause of prematurity and maternal mortality. Among the risk factors \nare PROM in prior pregnancies, genital/intrauterine tract infections, \nObstet Gynecol Int J. 2022;13(5):305‒309. 305\n©2022 Di Silvio-López et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, \nwhich permits unrestricted use, distribution, and build upon your work non-commercially.\nMesenchymal stem cells as an adjuvant for the \ntreatment of poi, and as a support in expectant \nmanagement of placental hematomas and premature \nrupture of membranes: case report\nVolume 13 Issue 5 - 2022\nDi Silvio-López Mauricio,1,2,3,6,7 Luján-\nIrastorza Jesús Estuardo,1,2 Durand-Montaño \nCarlos,1 Hernández-Ramos Roberto,1 Ávila-\nPérez Felipe de Jesús,1 Myslabodski Julio,8 \nPariente-Fernández Maruxa,1,2 Paredes-\nNúñez María Angélica,1,2 Pacheco-Pineda \nJosué Giovani,4 Vargas-Hernández Víctor \nManuel1,5 \n1Hospital Bité Médica, México\n2Clínica Helix, ciudad de México, México\n3Hospital MAC Periférico Sur, México\n4Instituto de T erapia Celular (ITC), Guadalajara, Jalisco, México\n5National Academy of Medicine México, México\n6Mexican Academy of Surgery, México\n7American College of Surgeons, International Fellow, USA\n8Banco de Cordón Umbilical (BCU), México\nCorrespondence: Luján Irastorza Jesús Estuardo, Managing \nDirector, Hospital Bité Médica, Clínica Helix, ciudad de México, \nMéxico, T el 5521292609, Email \nVargas Hernández Víctor Manuel, Managing Director, Hospital \nBité Médica, National Academy of Medicine México, México, T el \n5552179782, Email \nReceived: September 11, 2022 | Published: October 03, 2022\nAbstract\nIn Mexico, 17% of women of childbearing age have infertility problems, this alteration \nmay be associated to Premature Ovarian Insufficiency (POI). On the other hand, Premature \nRupture of Membranes (PROM) is defined as the rupture of ovular membranes before labor \nbegins. \nThe application of Mesenchymal Stem Cells (MSCs) has been proposed for the treatment \nof POI, placental abruption and PROM.\nObjective: Describe a case report of a patient that received MSCs by intravenous injection \nas an adjuvant for the treatment of POI, and as an aid to reduce placental hematomas that \nappeared during pregnancy, which resulted in PROM (preterm, and previable), and a \npreterm baby delivery (alive).\nClinical case presentation: A 30-year-old woman with history of primary infertility of \n2 years; Anti-Müllerian Hormone (AMH) of 0.2 ng/mL; laparoscopic Bilateral Tubal \nObstruction (BTO), endometriosis, diagnostic and surgical laparoscopy for myomatosis, \nand Factor VII deficiency; as well as 3 IVF, 4 embryo transfers, and 1 IUI unsuccessful. \nWith confirmed POI diagnosis, the application of several doses at different times of MSCS \nis decided, resulting in pregnancy. Sometime later during pregnancy, placental hematomas \nand PROM are observed and decided to apply MSCs at different stages of pregnancy, \nresulting in the live birth of a baby (29.3 Weeks of Gestation)\nConclusion: The application of multiple doses of MSCs turns more efficient the placental \ntissue restoration, allowing hematomas to disappear, and delaying a possible PROM. \nKeywords: mesenchymal stem cells, anti-Müllerian hormone, premature rupture, \nplacental hematomas\nObstetrics & Gynecology International Journal\nCase Report\n Open Access\n\n\nMesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in expectant \nmanagement of placental hematomas and premature rupture of membranes: case report\n306\nCopyright:\n©2022 Silvio-López et al.\nCitation: Di Silvio-López M, Luján-Irastorza JE, Durand-Montaño C, et al. Mesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in \nexpectant management of placental hematomas and premature rupture of membranes: case report. Obstet Gynecol Int J 2022;13(5):305‒309. \nDOI: 10.15406/ogij.2022.13.00668\nhemorrhages, hematomas, cervical anomalies, invasive procedures, \nsmoking, etc. The management of these patients depends on the fetal \nmaturity. There are 2 types of management: \n1) Labor, it is recommended for full-term pregnant women with 37 \nor more WG, with no complications \n2) The expectant management consisting of hospitalization to \nmonitor for a period of time the risk of infection, placental \nabruption, umbilical cord compression, fetal wellbeing and \nlabor.23 \nIn the case of POI, there are many situations where the only \noption for the patient to get pregnant is to accept egg donation, 24,25 \nsituation that is not well received by some couples, and as there are \nno treatment that restores ovarian function, some medical specialists \nhave been prompted to investigate new treatment alternatives. En \nexample of this is the direct application of mesenchymal stem cells \n(MSCs) via intravenous injection or directly into ovaries. Similarly, \nintravenous application of MSCs has been proposed for the treatment \nof placental abruption and PROM when they are caused by the \npresence of hematomas.26  \nBecause of their high proliferation rate, regeneration, and high \ndegree of differentiation into different cell types through asymmetric \ndivisions,27,28 MSCs in recent years have been considered as a new \noption to be used in regenerative medicine. MSCs may be obtained \nfrom embryonic and extraembryonic tissue, as well as from adult \norgans, some of which are bone marrow, peripheral blood, umbilical \ncord, adipose tissue, etc.; in addition, they may be autologous or \nfrom donor (allogenic). Their application in clinical research has \nbeen as a cellular therapy for conditions such as Alzheimer, lateral \namyotrophic sclerosis, Huntington disease, Parkinson disease, \ncerebral and myocardial infarctions, medullar damage, immune \ndisturbances, arthrosis, restoration of ovarian function, reduction \nof cerebral hematomas, etc. They release a wide selection of \ncytokines, chemokines, and growth factors, with anti-apoptotic, anti-\ninflammatory, proangiogenic, and immunomodulating characteristics; \nadditionally, they are an aid in tissular restoration and replacement \nof damaged cells, which makes them highly attractive for clinical \napplication.29–32 \nThe following is a case report of a patient that received MSCs by \nintravenous injection as an adjuvant for the treatment of POI, and as \nan aid to reduce placental hematomas that appeared during pregnancy, \nwhich resulted in PROM (preterm, and previable), and a preterm baby \ndelivery (alive).\nCase report\nA 30-year-old woman with history of primary infertility of 2 \nyears; AMH, 1,9; laparoscopic Bilateral Tubal Obstruction (BTO), \nendometriosis, diagnostic and surgical laparoscopy for myomatosis, \nand Factor VII deficiency; as well as 3 IVF, 4 embryo transfers, and \n1 IUI unsuccessful, attended the PRONATAL Clinic because she \nwanted to get pregnant; where, after a background check, a Controlled \nOvarian Stimulation (COS) was started with long protocol. It began \nthe 21st day of the previous cycle with Lucrin, 20 IU/24h for 3 days; \nthen, 10 IU/24h, and stopping on the first day of menstruation. That \nday the application of Merapur, 300IU was started from Day 1 \nto Day 11, and Choragon, 10000IU on Day 12. Eight MII oocytes \nwere obtained by follicular aspiration, from which 1 developed into \nblastocyst (BH/BB, euploid), and 7 degenerated.\nTherefore, the euploid blastocyst was vitrified and it was decided \nto accumulate oocytes, which was not possible because the patient \npresented a spontaneous pregnancy [Retained Dead Egg (RDE) of \n10.3WG], where the loss was attributed to inflammation by increased \nimmunity as the patient showed an increment of Natural Killers (NK) \ncells (12%) in peripheral blood, and Tumour Necrosis Factor alpha \n(TNF-α) G308A (heterozygote), TNF-α G238A (homozygote) and \nLymphotoxin-alpha (LT-α) A252G (heterozygote) polymorphism. So, \na treatment was established with Lite vaccination (immunotherapy \nwith paternal lymphocytes), and Enbrel (treatment for autoimmune \ndiseases). \nBefore starting another COS, it was decided to evaluate AMH \nagain, showing a decrease from 1.9 to 0.2ng/mL, which confirmed \nPOI diagnosis. Then, it was decided to carry out a COS by DuoStim \nat low doses of Pergoveris daily, and the application of MSCs directly \nin ovary, and systemically (intravenous injection by the end of the \nsecond stage of DuoStim). The first stage began with Pergoveris daily, \n150IU/75IU from Day 3 to Day 9; Cetrotide, 0.25mg/day on Days \n8 and 9; and Ovidrel, 250µg on Day 9. Three oocytes (MII) were \nobtained, which were fertilized with semen of the partner diagnosed \nwith Normozoospermia, from which none developed into blastocyst. \nThe second stage of DuoStim began with Pergoveris daily, \n150IU/75IU from Day 15 to Day 21; Cetrotide, 0.25mg/day from \nDay 18 to Day 21; and Ovidrel, 250µg on Day 21. The day of \nfollicular aspiration 4 oocytes were obtained, from which 3 were \nMII. These, when fertilized with semen of the partner diagnosed with \nnormozoospermia, did not developed into viable blastocysts. At the \nend of the second stage of DuoStim, after obtaining the last oocyte, \n15 million of Adipose tissue derived mesenchymal stem cells (AD-\nMSCs) diluted in 3mL of Hartman’s solution (4mL of total vol.) were \napplied directly in ovaries as an adjuvant for the treatment of POI. \nAlso, 30 million of AD-MSCs diluted in 8 mL of Hartman’s solution \nwere applied systemically (intravenous injection). A total of 60 \nmillion of AD-MSCs were applied, which were kindly provided by \nthe Cellular Therapy Institute (ITC, Guadalajara, Mexico) (Figure 1).\nFigure 1 T echnique; Application of AD-MSCs in the ovary; 1) The aspiration \nsystem is closed to prevent AD-MSCs from going to the oocyte collection \ntube; 2) AD-MSCs were injected with the flow of the system directed to the \novary, and 3) It is observed whether AD-MSCs are deposited in the ovary.\nAs the effects of MSCs on ovaries may be observed 2 months \nafter their application; 33 within this waiting period, it was decided \nto transfer the embryo (BH/BB, euploid) obtained in the first cycle \ncarried out in PRONATAL Clinic, which, when devitrified, did not \nrecover well, starting a state of degeneration and cell death resulting \nin the cancellation of the procedure. This situation disappointed \nthe patients, who decided not to wait for the AD-MSCs to have the \nexpected effect and decided to carry out a cycle with egg donor, where \n\n\nMesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in expectant \nmanagement of placental hematomas and premature rupture of membranes: case report\n307\nCopyright:\n©2022 Silvio-López et al.\nCitation: Di Silvio-López M, Luján-Irastorza JE, Durand-Montaño C, et al. Mesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in \nexpectant management of placental hematomas and premature rupture of membranes: case report. Obstet Gynecol Int J 2022;13(5):305‒309. \nDOI: 10.15406/ogij.2022.13.00668\n22 donor oocytes were fertilized with semen of the husband (mild \nteratozoospermia). Five blastocysts were obtained, from which 3 were \nvitrified, and 2 were transferred fresh, resulting in a twin pregnancy.\nAfter the patient was able to achieve pregnancy, she had bleeding \nthroughout the first trimester (spotting every other day) since she \nimplanted the embryo.\nAt 9.3 WG, during obstetrical review an RDE of tween B (Figure \n2B), and a 4cm-hematoma in the placenta of embryo A (Figure 2A) \nwere observed; so, it was decided to apply an intravenous injection \nof 60 million umbilical cord-mesenchymal stem cells (UC-MSCs) \n[Kindly provided by the Bank of Umbilical Cord of México (BCU)] \nas an adjuvant to reduce the size of the hematoma.\nFigure 2 Ultrasound of tween pregnancy (9.3 WG).  A) Fetus A (hematoma), \nand B) Fetus B (RDE).\nAfter application of UC-MSCs, the hematoma was reduced to: \n2.41cm (9.5WG), 1.5cm (9.6WG), and 0.8cm (10, and 10.1WG). At \n10.1 WG, 35 million UC-MSCs [Kindly provided by the BCU] were \napplied by intravenous injection as a booster, achieving complete \ndisappearance of the hematoma at 11.5WG (Figure 3).\nFigure 3 Ultrasound of singleton pregnancy after RDE of Fetus B, in addition \nto the presence of hematoma that was reduced after application of AD-MSCs.  \nHematoma size:  A) 4 cm (9.3 WG); b) 2.41 cm (9.5 WG), and C) 0.8 cm (10, \nand 10.1 WG).\nAt 16.1 WG, the patient arrives to the emergency room, reporting \nactive transvaginal bleeding after sexual intercourse. A suitable \nimplantation was observed by ultrasound; in the upper pole there is an \nimage of hematomas of 1.5 and 1.2cm. In the same way as in week 9.3, \nthe application of UC-MSCs [Kindly provided by the BCU] was made \nby intravenous injection, as an alternative to reduce hematomas. At \n16.3 weeks of gestation, after application of AD-MSCs, hematomas \nwere reduced to 0.4 cm, and 0.3 cm; at 17.6WG no hematomas are \nobserved (Figure 4). \nFigure 4  Ultrasound of pregnancy; A) 16.1 WG, 2 small hematomas are \nobserved (1.5 and 1.2 cm), and B) 17.6 WG, with no presence of hematomas.\nAt 23.2WG, the patient returns to PRONATAL Clinic because \na day before she presented red spotting after sexual intercourse \n(no hematomas are observed). At 28.3WG, the patient reports fluid \nleakage at night and together with medical history, nitrazine and \ncrystallography test, confirming PROM, therefore, conservative \nmanagement (expectant) is followed, and 60 million UC-MSCs \n[Kindly provided by the Bank of Umbilical Cord of México (BCU)] \nare applied at 29WG.\nAfter application of UC-MSCs at 29.2WG, the lung maturation \nis completed. Patient’s vital signs are stable, amniotic fluid remained \nstable, hemodynamic parameters normal, and with no data of maternal \nor fetal inflammatory response. For that moment no maternal or fetal \nemergency indicated immediate termination of pregnancy; therefore, \nit was suggested to continue with the conservative management of \nPROM. Finally, at 29.3WG, cesarean section was performed with the \nfinding of a male birth with 1340g, 41cm, and Apgar 8/9. The child is \ncurrently in the first year of life.\nDiscussion\nCurrently, a large number of studies have shown how MSCs help to \nreduce the symptoms and alterations observed in different pathologies \nthrough animal models and clinical trials. This, in turn, has allowed the \ndevelopment of increasingly refined MSCs procurement techniques \nwith ability to isolate such cells from different tissues. In the case \nof POI, studies of MSCs transplantation have demonstrated their \ntherapeutic potential by restoring ovarian structure and function.34 An \nexample of this is reported by Luján J. et al.,33 who, in a retrospective \nstudy that included 8 patients with POI, observed that the application \nof AD-MSCs increased mean values when the endometrial thickness \n(8.6 to 9.4mm), the number of oocytes (2 to 9), and their size (13.5 to \n15.5mm) were evaluated on Day 11 of menstrual cycle. This allowed to \nobtain a greater number of MII oocytes (2.6 to 4.2) the day of follicular \naspiration, and blastocysts (0 to 3) thereafter.33 Herraiz S. et al.,35 in a \ngroup of 17 patients who were poor responders, observed that after \napplication of 50 x 106 BM-MSCs in the ovary by catheterization from \nDay 2 to Day 43, the number of antral follicles was increased (3 vs 8). \nLuján J. et al.,2 in a case report of a woman (39 years old) diagnosed \nwith POI, reported that the application of AD-MSCs (intra-ovarian) \nincreased the mean number of MII oocytes obtained (3 to 14); also, \nHerraiz S. et al.,36 reported an increase of the number of MII obtained \n(15 vs 30) in immunodeficient mice with ovarian damage induced by \nchemotherapy, after the application of BM-MSCs; and Li J. et al., 37 \nin a group of female mice with POI induced by cyclophosphamide, \nshowed an increased number of follicles (11 vs 13) after 6 weeks \nof application of MSCs from chorionic plate. Unfortunately, in the \npresent work the patients decided not to wait the 2 months indicated in \nstudies before the effects of the application of AD-MSCs can be seen, \naccepting egg donation. \nOn the other hand, in this report the patient developed placental \nhematomas twice after achieving pregnancy by egg donation. The \nfirst one at 9.3 weeks of gestation, that was reduced and disappeared \napproximately at 11.5WG, after application of UC-MSCs. Similarly, \nat 16.1WG, two hematomas were observed (1.5, and 1.2cm), which \nalso reduced their size and disappeared at 17.6 WG, after application \nof UC-MSCs. In addition, PROM was present at 28.3WG, and the \npatient was kept under PROM expectant management. Immediate \napplication of UC-MSCs was carried out, which probably allowed \nto delay delivery up to the 29.3 WOG, and to complete the lung \nmaturation. Similarly, in a case report by Luján J. et al., 2020, a \nretro placental hematoma was observed at 25 weeks of gestation \n(2.8x2.1x0.6cm), which, after 3 applications of AD-MSCs (1st: 25 \n\n\nMesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in expectant \nmanagement of placental hematomas and premature rupture of membranes: case report\n308\nCopyright:\n©2022 Silvio-López et al.\nCitation: Di Silvio-López M, Luján-Irastorza JE, Durand-Montaño C, et al. Mesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in \nexpectant management of placental hematomas and premature rupture of membranes: case report. Obstet Gynecol Int J 2022;13(5):305‒309. \nDOI: 10.15406/ogij.2022.13.00668\nWOG, 2nd: 26.5 WOG, and 3rd: 27.4WG) was reduced, confirming \nrepair of placental abruption at 28.2 WOG, and resulting in live \nbirth of newborn at 30.1 WOG. This could be due to the fact that the \napplication of MSCs improves the microenvironment surrounding the \ndamaged tissue (hematoma), thus stimulating the generation of new \nblood vessels, regulating the immune response and preventing cell \ndeath by apoptosis, by producing cytokines and growth factors that \nregulate these processes, in addition to replacing the damaged tissue \nwith new tissue by differentiating.38–41 \nFinally, there are very few reports of MSCs application in humans, \nand the mechanisms proposed about how they function have been \ndeveloped through studies on laboratory animals, which make these \nprocedures an area of opportunity in clinical practice for the study \nof diverse pathologies such as POI, and PROM, areas in which it \nis necessary to carry out randomized, controlled trials with large \nsamples.\nConclusion\nMSCs transplant studies have demonstrated their therapeutical \npotential for restoration of ovarian structure and function. \nUnfortunately, in this work the patients’ decision to accept egg \ndonation after Application of AD-MSCs, prevented us from seeing \nthe potential benefits of AD-MSCs as an adjuvant for the treatment \nof POI.\nThe application of multiple doses of UC-MSCs (by intravenous \ninjection) turns more efficient the placental tissue restoration, allowing \nhematomas to disappear, and delaying a possible PROM. This makes \nit possible to finalize, as in this case, the lung maturation.\nFinally, conservative treatment for placental hematomas and \nPROM is currently limited, and there is no complementary therapy \nbeyond maternal and fetal surveillance. Therefore, we suggest the \ndevelopment of a protocol for the application of MSCs in PROM, to \nconfirm reproducibility of research findings and to be able to establish \nthis measure as a standard therapeutic option.\nAcknowledgments\nNone.\nFunding \nNone.\nConflicts of interest \nAuthor declares there is no conflict of interest exists.\nReferences\n1. Corona T, Halabe J, Vázquez G. Academia Nacional de Medicina de \nMéxico. 2019.\n2. Lujan J, Guerrero J, Kava B, et al. Autologous mesenchymal stem cell \ntherapy in patients with unexplainable low ovarian response: first case \nin Mexico. Journal of Medical & Advanced Clinical Case Reports . \n2020;2(1):1–4. \n3. Eftekhar M, Aflatoonian A, Mohammadian F, et al. Adjuvant growth \nhormone therapy in antagonist protocol in poor responders undergoing \nassisted reproductive technology. Archives of Gynecology and \nObstetrics. 2013;287(5):1017–1021. \n4. Eftekhar M, Sadat E, Tabibnejad N. Outcome of reproductive \ntechnology in different subgroups of poor ovarian responder fulfilling \nthe POSEIDON Criterian, Middle East. Fertility Society Journal . \n2018;23(4):399–403. \n5. Santoro N. Mechanisms of premature ovarian failure. Ann Endocrinol \n(Paris). 2003;64(2):89–92. \n6. Timmreck L, Reindollar R. Contemporary issues in primary amenorrhea. \nObstet Gynecol Clin North Am. 2003;30(2):287–302. \n7. Beck P, Persani L. Premature ovarian failure. Orphanet J Rare Dis . \n2006;1(9):1–5. \n8. Kumar N, Manesh I. Premature ovarian insufficiency atiology and long–\nterm consequences. Women’ s Health. 2017;3(2):45–58. \n9. Luborsky J, Meyer P, Sowers M, et al. Premature menopause in a \nmulti–ethnic population study of the menopause transition. Human \nReproduction. 2003;18(1):199–206. \n10. Warren B, Kinsey W, Mcginnis L, et al. Ovarian autoimmune disease: \nclinical concepts and animal models. Cellular & Molecular Immunology. \n2004;11:510–521. \n11. Kumar M, Pathak D, Venkatesh S, et al. Chromosomal abnormalities & \noxidative stress in women with premature ovarian failure (POF). Indian \nJ Med Res. 2012;135:92–97. \n12. Huang W, Cao Y , Shi L. Effects of FSHR polymorphisms onpremature \novarian insufficiency in humanbeings: a meta–analysis. Reproductive \nBiology and Endocrinology. 2019;17(80):1–6. \n13. Cho H, Lee S, Min K, et al. Advances in the treatment and prevention of \nchemotherapy–induced ovarian toxicity. Int J Mol Sci. 2020;21(20):7792. \n14. Buigues A, Marchante M, Herraiz S, et al. Diminished ovarian \nreserve chemotherapy–induced mouse model:a tool for the preclinical \nassessmentof new therapies for ovarian damage. Reprod Sci. 2019:1–11. \n15. Iwase A, Nakamura T, Nakahara T, et al. Assessment of ovarian reserve \nusing anti–Müllerian hormone levels in benign gynecologic conditions \nand surgical interventions: a systematic narrative review. Reprod Biol \nEndocrinol. 2014;12(125):1–8. \n16. Persani L, Rossetti R, Cacciatore C. Genes involved in human premature \novarian failure. J Mol Endocrinol. 2010;45(5):257–279. \n17. Welt C. Primary ovarian insufficiency: a more accurate term for \npremature. Clinical Endocrinology (OXFORD). 2008;68(4):499–508. \n18. Kodaman P. Early menopause: primary ovarian insufficiency and surgical \nmenopause. Seminars in Reproductive Medicine. 2010;28(5):360–369. \n19. Torrealday S, Kodaman P, Pal L. Premature Ovarian Insufficiency \n– an update on recent advances in understanding and management. \nF1000Res. 2017;6:1–15. \n20. Baber R, Panay N, Fenton A. IMS Recommendations on women’s \nmidlife health and menopause hormone therapy. Climacteric. \n2016;19(2):109–150. \n21. Cox L, Liu J. Primary ovarian insufficiency: an update. Int J Womens \nHealth. 2014;6:235–243. \n22. Dragojević S, Vasiljević M, Jovanović A, et al. Premature ovarian \ninsufficiency – novel hormonalapproaches in optimizing fertility. \nGynecol Endocrinol. 2019;36(2):1–4. \n23. Orias M. Premature Rupture of Membranes. Revista Médica Sinergia . \n2020;11(e606):5. \n24. Obinchemti T, Youta C, Bebey B, et al. Successful pregnancy with \ndonor eggs in–vitro fertilization after premature ovarian insufficiency \nin a tertiary hospital in a low–income setting: a case report. Fertil Res \nPract. 2016;2(12):1–6. \n25. Chae J, Gavrilova L. Premature ovarian insufficiency: procreative \nmanagement and preventive strategies. Biomedicines. 2018;7(2):1–10. \n26. Lujan J, Durand C, Hernandez R, et al. Endovenous application of \nalogenic AD–MSCs as therapy for abruptio placentae: a case report. \nGlobal Research in Gynecology and Obstetrics. 2020;2(2):12–15. \n\nMesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in expectant \nmanagement of placental hematomas and premature rupture of membranes: case report\n309\nCopyright:\n©2022 Silvio-López et al.\nCitation: Di Silvio-López M, Luján-Irastorza JE, Durand-Montaño C, et al. Mesenchymal stem cells as an adjuvant for the treatment of poi, and as a support in \nexpectant management of placental hematomas and premature rupture of membranes: case report. Obstet Gynecol Int J 2022;13(5):305‒309. \nDOI: 10.15406/ogij.2022.13.00668\n27. Frese L, Dijkman P, Hoerstrup S. Adipose tissue–derived stem cells in \nregenerative medicine. Transfus Med Hemother. 2016;43(4):268–274. \n28. Tsuji W, Rubin J, Marra K. Adipose–derived stem cells: Implications in \ntissue regeneration. World J Stem Cells. 2014;6(3):312–321. \n29. Elfayomy A, Almasry S, El–Tarhouny S, et al. Human umbilical cord \nblood–mesenchymal stem cells transplantation renovates the ovarian \nsurface epithelium in a rat model of premature ovarian failure: possible \ndirect and indirect effects. Tissue Cell. 2016;48:1–13. \n30. Ghadami M, El–Demerdash E, Zhang E, et al. Bone marrow \ntransplantation restore follicular maturation and steroid hormones \nproduction in a mouse model for primary ovarian failure. PLoS One . \n2012;7:e36462. \n31. Shammaa R, El–Hakim A, Abusarah J, et al. Mesenchymal stem cells \nbeyond. Frontiers in Cell and Developmental Biology. 2020;8(72):1–17.\n32. Afflerbach A, Kiri M, Detinis T, et al. Mesenchymal stem cells as \na promising cell source for integration in novel in vitro models. \nBiomolecules. 2020;10(1306):1–30. \n33. Luján J, Durand C, Hernández R, et al. Therapeutic potential of \nautologous adipose derived mesenchymal stem cells in human poi and \novarian aging. Journal of Evolving Stem Cell Research. 2021;1(3):5–18. \n34. Fazeli Z, Abedindo A, Davood M, et al. Mesenchymal Stem Cells \n(MSCs) therapy for recovery of fertility: a systematic review. Stem Cell \nRev Rep. 2017;14(1):1–12. \n35. Herraiz S, Romeu M, Buigues A. Autologous stem cell ovarian \ntransplantation to increase reproductive potential in patients who are \npoor responders. Fertil Steril. 2018;10(3):496–505. \n36. Herraiz S, Buigues A, Diaz C. Fertility rescue and ovarian follicle \ngrowth promotion by bone marrow stem cell infusion. Fertility and \nSterility. 2018;109(5):908–918. \n37. Li J, Yu Q, Huang H, et al. Human chorionic plate–derivedmesenchymal \nstem cells transplantationrestores ovarian function in achemotherapy–\ninduced mouse model ofpremature ovarian failure. Stem Cell Res Ther. \n2018;9(81):1–9. \n38. Rudolf A, Hendrik M. Immunomodulation by Mesenchymal Stem Cells \n(MSCs): mechanisms of action of living, apoptotic, and dead MSCs. \nFront Immunol. 2019;10(1191):1–10. \n39. Maacha S, Sidahmed H, Jacob S, Gentilcore G, et al. Paracrine \nmechanisms of mesenchymal stromal cells in angiogenesis. Stem Cells \nInt. 2020:1–20. \n40. Guiducc S, Porta F, Saccardi R, et al. Autologous mesenchymal stem \ncells foster revascularization ofischemic limbs in systemic sclerosis. Ann \nIntern Med. 2010;153(10):650–654. \n41. Lian B, Chen J, Li T, et al. Clinical remission of a critically ill COVID–\n19patient treated by human umbilical cordmesenchymal stem cells. \nMedicine. 2020;99(31):1–6.","source_license":"CC0","license_restricted":false}