Search

Nowadays, sirolimus as a popular immunosuppressant has been frequently used to shield the organ transplant recipients from immunological rejection. The immunomodulatory effects of sirolimus in the female reproductive process have been demonstrated by ongoing medical study. By blocking the immune-regulating action of mammalian target of rapamycin, sirolimus may help those patients with recurrent implantation failure, recurrent spontaneous abortion, endometriosis, chronic endometritis, polycystic ovary syndrome, and other illnesses of the reproductive system. Additionally, sirolimus can enhance the rates of embryo implantation and clinical pregnancy in individuals with aberrant immunological statuses at the mother-fetal interface, reduce ovarian hyperstimulation syndrome during assisted reproductive treatment, and improve the pregnancy outcomes. A review was conducted on the mode of action, research status and safety of sirolimus in female reproductive disorders. [ABSTRACT FROM AUTHOR]

In assisted reproductive technology, it is very important to prevent the premature endogenous luteinizing hormone (LH) peak in process of controlled ovarian stimulation. Traditional controlled ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) analogues (GnRH agonists or antagonists) to inhibit the level of endogenous LH have many disadvantages such as high cost and inconvenient use. Progestin-primed ovarian stimulation (PPOS) protocol has been proved to achieve good clinical outcomes in various populations by the negative feedback effect of exogenous progesterone on pituitary gland to inhibit LH level, and its offspring safety has also been preliminarily confirmed. In this paper, the mechanism of PPOS, application of different exogenous progesterone drugs, application effects of different populations and offspring safety of PPOS were reviewed. [ABSTRACT FROM AUTHOR]

Twin reversed arterial perfusion sequence (TRAPS) is a rare and severe complication of monochorionic twin pregnancies, due to abnormal placental-fetal vascular anastomosis, which is characterized by absence of heart or loss of normal cardiac structure in one twin. We reported a case of triplet pregnancy complicated by TRAPS after assisted reproductive technology. Two cleavage-stage frozen embryos were transferred, one of which developed into monochorionic twin pregnology. The TRAPS was diagnosed by ultrasound at 8 +5 weeks. However, due to personal factors, the patient did not intervene in a timely manner and the pump twin died. Another single fetus developed normally until full term delivery. If the treatment is needed, as for the technique of choice to interrupt the vascular supply to the acardiac twin, the radiofrequency ablation of the intrafetal vessel is usually the preferred approach. However, the best timing of intervention is still debated. [ABSTRACT FROM AUTHOR]

Since the first successful use of oocyte cryopreservation and resuscitation, to obtain twin pregnancies, in 1986, oocyte cryopreservation has gradually become an intervention measure for iatrogenic ovarian dysfunction. In recent years, the number of patients with diminished ovarian reserve (DOR) has shown an increasing trend, and the preservation of their fertility is receiving increasing attention. The iatrogenic influencing factors of DOR mainly include reproductive system surgery, tumor radiotherapy and chemotherapy, etc. Oocyte cryopreservation is a first-line treatment option for fertility preservation, and its safety, applicability, utilization rate, and egg donation treatment in the clinical application of iatrogenic DOR patients have been confirmed by clinical data and relevant literature. However, the issues related to the timing of oocyte cryopreservation, limitations of clinical application and ethical policies cannot be ignored. Oocyte cryopreservation is of great significance for improving the pregnancy outcomes of unmarried patients with iatrogenic DOR and the reproductive autonomy of married patients. After clarifying the iatrogenic influencing factors of DOR, it is recommended to seek consultation from multiple disciplines such as oncology, gynecology and reproductive health as soon as possible to develop the personalized oocyte cryopreservation plans. [ABSTRACT FROM AUTHOR]

Epidemiologists indicate that about half of the couple’s infertility cases are due to a male factor. Despite this, the role of andrologists or endocrinologists in assisted reproductive technique (ART) centers is still underestimated. According to our literature review, this reduces the chance of a thorough clinical evaluation of the male partners, which, sometimes consists only in a mere semen analysis, usually performed by laboratory technicians. A more complete diagnostic process could lead to the identification of potentially treatable causes of infertility, the recognition of diseases that require immediate treatment, and to the discovery of genetic diseases and, therefore, transmissible to the offspring. It can also increase the success rate of ART resulting in less psychological and financial burden for both public health resources and infertile couples. The presence of medical personnel with andrological and endocrinological skills in the ART centers represents the first step in creating ‘precision medicine’. We hope that the guidelines of the various scientific societies will clearly contemplate this possibility. [ABSTRACT FROM AUTHOR]

The platelet-rich plasma (PRP) is a concentrate extracted from whole blood centrifugation at a platelet concentration of up to 7 times that of circulating serum, being rich in growth factors and cytokines. Some of factors promote tissue healing and regeneration by inducing chemotaxis, cell migration and differentiation. Ovarian reserve refers to the quality and quantity of eggs retained in ovaries, which is an important indicator of female fertility potential. Based on the current basic research and clinical trials at home and abroad, it is proposed that PRP can promote ovarian vascular production, reduce apoptosis of granule cells and atresia of follicles, promote cumulus dilation, increase mitochondrial activity pathway and promote oocyte development. This review may provide a theoretical basis for the clinical practice of PRP in the assisted reproduction of those women with the reduced ovarian reserve. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals (EDC) are exogenous compounds, which can interfere with the hormones action and endocrine pathways, affect the development of female reproductive system and ovarian function, and therefore EDCs are associated with female infertility. Current research mainly focus on EDC exposure and its correlation with the different diseases of the endocrine axes. Studies have shown that EDCs affect female fertility by causing ovarian dysfunction, follicular development abnormality, endometrial receptivity reduction, and embryo quality decline, as well as the lowed clinical outcome of assisted reproduction in infertile women. Accumulating evidence in animal studies has provided important insights into the mechanism of EDC effects. This review summarizes some of the most common EDCs including pesticides, bisphenol A and phthalates, and the effects of EDCs on female fertility and clinical outcomes of assisted reproductive technology. [ABSTRACT FROM AUTHOR]

Cesarean scar defect (CSD) is one of the common complications after cesarean section. The clinical manifestations include abnormal uterine bleeding, pelvic pain and secondary infertility. With the evolution of fertility policy and the increase of cesarean section rate, the infertility associated with it is gradually gaining attention. There is no consensus on the treatment options of infertility secondary to CSD currently. In patients combined with small amounts of uterine cavity effusion, the prolonged GnRHa down-regulation protocol can be used to assist reproduction. While in patients with abnormal uterine bleeding or obvious endometrial cavity fluid, surgery should be considered as first-line treatment. However, there is still a lack of uniformity in the choice of surgical approach and surgical plans are usually determined based on the residual myometrial thickness on the scar. In addition, treatment options such as intrauterine ozone infusion, traditional Chinese medicine conditioning and physiotherapy, and stem cell transplantation may also have potential benefits in the treatment of secondary infertility in CSD. [ABSTRACT FROM AUTHOR]

Whether the artificial intervention of assisted reproductive technology (ART) in the early life will bring potential risks to the long-term health and safety of the offspring has always been a key issue of human health. This article reviews the key points of ART, such as artificial insemination, in vitro fertilization -embryo transfer and its derivative technology, and summarizes and analyzes the safety of offspring from the aspects of adverse pregnancy outcomes, birth defects, long-term health problems, and genetic imprinting abnormalities. Most studies support the safety of ART and believe that children born by ART do not increase the incidence of adverse events. However, since most research data focus on infants and young children, it is still necessary to conduct the long-term health follow-up of children born by ART to obtain health data in adolescents and adulthood, and to further demonstrate the safety of children born by ART. [ABSTRACT FROM AUTHOR]

The ovarian hyperstimulation syndrome (OHSS) complicated with superior mesenteric venous thrombosis (SMVT) and portal vein thrombosis (PVT) is a rare thrombotic disease, with the continuous increase of human chorionic gonadotropin in pregnant women and the further aggravated condition. In severe cases, intestinal ischemic hemorrhage, septic shock, abortion, premature delivery and death may occur. Therefore, it is one of the serious complications in the process of in vitro fertilization -embryo transfer (IVF -ET). The early clinical manifestations and auxiliary examinations of the disease are lack of specificity, and it is easy to be misdiagnosed or missed, and to delay treatment. A case of OHSS found 10 days after IVF-ET and diagnosed with SMVT and PVT complicated with intestinal obstruction 61 days after transplantation was reported. After multidisciplinary consultation, the comprehensive treatment of oxygen inhalation, expansion of blood volume, anticoagulation, infection prevention, correction of electrolyte disorders and others was given. The effect was poor and the condition deteriorated sharply. After transferred to our hospital, the emergency resection of necrotic small intestine plus end-to-end anastomosis of residual small intestine plus thrombectomy of superior mesenteric vein and portal vein was performed. At more than 5 months of pregnancy, induction of labor was performed due to fetal death. [ABSTRACT FROM AUTHOR]

The provision of care that is responsive to the preferences, needs and values of gamete donors is key to improving their recruitment and ensuring the functioning of gamete banks. This qualitative study aimed to explore gamete donors' experiences about the facilitating and constraining human and system factors to donor-centred healthcare delivery in gamete banks. It is based on 20 semi-structured interviews with oocyte and sperm donors, recruited at the Portuguese Public Bank of Gametes, conducted from November 2017 to February 2019. Deductive content analysis was performed using the software NVivo12, following the patient-centred infertility care model. Interviewees identified facilitating factors mostly related with the human dimension of care (i.e. careful and available attitude and behaviours of health professionals, as well as their good communication skills and emotional support). Constraining factors were predominantly identified at the system level (i.e. insufficient information provision, poor coordination, and integration). Lack of privacy emerged simultaneously as a human and a system constraining factor (i.e. physical discomfort during medical-technical acts or gamete collection). There is room for improving clinical practice and the organisation of healthcare services within a context where the competence and attitude of, and relationship with, the staff are highly valued. [ABSTRACT FROM AUTHOR]

The research related to the detrimental effect of COVID -19 has not been limited in the respiratory system, but it gradually expanded to other important systems. Several studies demonstrated that SARSCoV-2 recognized the angiotensin converting enzyme 2 (ACE2) receptors in human tissues and organs, thereby causing damages to the structure and function of human systems including reproduction. For male reproductive system, SARS-CoV-2 affects the function of hypothalamic-pituitary-gonad (HPG) axis, damages the spermatogenic process and decreases sperm quality. For female reproductive system, SARS-CoV-2 also disturbes the function of HPG axis. Considering the pregnant women infected with the virus, the rate of severe diseases was low and the rehabilitation was good, but adverse pregnancy outcomes may also occur. The impact of SARS-CoV-2 on assisted-reproduction is mild, but it could be a risk factor of pulmonary and renal complications when the patient suffered from ovarian hyperstimulation syndrome during ovulation induction. In addition, there is no evidence to show the obvious negative effect of various SARS -CoV-2 vaccines on the reproductive system. However, mental health problems such as the decreased fertility intention caused by the COVID-19 pandemic still need to be further investigated. [ABSTRACT FROM AUTHOR]

Ovarian hyperstimulation syndrome is a common complication in assisted reproductive technology. It usually occurs after two weeks or more of induced ovulation. However, the spontaneous ovarian hyperstimulation syndrome (sOHSS) is extremely rare. Some clinical cases showed that the etiology of sOHSS was related to the mutations of follicle stimulating hormone receptor gene, the high level of human chorionic gonadotropin (hCG), the high level of thyroid-stimulating hormone (TSH), and gonadotropin pituitary adenoma. In this paper, we report a case of twin pregnancy complicated with sOHSS, and further study the possible etiology, diagnosis and treatment of sOHSS. [ABSTRACT FROM AUTHOR]

A case of pregnancy combined with pelvic abscess after oocyte retrieval and IVF -ET in a patient with ovarian endometriotic cyst was reported. This patient aged 24 years, with infertile for 4 years and polycystic ovary syndrome for 1 year, underwent vaginal ovarian cyst puncture. Diane-35 menstruation treatment was given for 1 cycle. After preoperative examination, assisted reproductive treatment was performed. After 10 days of ovulation extraction and IVF -ET, patient suffered from abdominal pain and fever. After anti -inflammatory therapy failed, laparoscopic exploration was performed, pelvic abscess and acute pelvic inflammation were diagnosed. After that, the pelvic abscess removal and drainage were performed again. Intravenous anti - inflammatory was given after the operation. The patient was cured and discharged. The data of this case were analyzed, and 8 cases of pelvic abscess after assisted reproduction were combined and reviewed, in order to improve the understanding of related complications after assisted reproduction. Infertile patients with ovarian endometriotic cyst were more likely to develop pelvic abscess after oocyte retrieval in the past. In addition, chronic pelvic inflammatory disease, vaginitis and the history of repeated operations are of three risk factors of pelvic abscess. The main clinical manifestations of pelvic abscess are abdominal pain and fever. Patients should be treated actively once diagnosed. If antibiotic treatment failed, surgical treatment should be considered in time. [ABSTRACT FROM AUTHOR]

Vitamin D not only participates in the calcium and phosphorus metabolism and the skeletal homeostasis as a steroid hormone, but also plays a role as a reproductive hormone. In women, vitamin D is involved in follicular formation and the production of ovarian sex hormones, which affects ovarian reserve function. In men, it can affect semen quality and sperm motility. Vitamin D receptor is widely expressed in the reproductive organs of both sexes, which can affect the fertility and pregnancy outcome of assisted reproductive technology through a variety of mechanisms. However, there is no consensus on whether exogenous vitamin D supplementation improves pregnancy outcomes of infertile patients undergoing assisted reproductive technology. This paper reviews the effect of vitamin D on male and female reproductive function, and discusses whether vitamin D can improve the outcome of assisted reproductive technology. [ABSTRACT FROM AUTHOR]

Purpose: Relugolix is an oral gonadotropin‐releasing hormone antagonist (GnRHant), which was first introduced in 2019. This study investigated the effects of the conventional injectable GnRHant formulation and this new oral GnRHant formulation on controlled ovarian stimulation (COS) cycles. Methods: Relugolix was administered in 126 cycles and conventional GnRHant injection was administered in 658 cycles (controls). The follicle stimulation was performed by an antagonist method, and for final oocyte maturation, recombinant human chorionic gonadotropin (rHCG), or gonadotropin‐releasing hormone agonist (GnRHa), or both (dual trigger) were selected. The number of retrieved oocytes was counted and then they were evaluated for subsequent development up to cleavage stage. Results: The number of retrieved oocytes which was the primary outcome of this research was affected by the combination of GnRHant type and the final oocyte maturation agent. The combination of relugolix and a GnRHa trigger showed a significantly lower number of retrieved oocytes (p < 0.001) than the other combinations. Conclusions: Relugolix is a new option for COS cycles, but should be carefully combined with the final maturation agent. Clinical trial approval: This study was conducted after approval by the Medical Corporation Sankeikai Institutional Ethics Committee (approval number: 2019‐34). [ABSTRACT FROM AUTHOR]

Sperm DNA fragmentation (SDF) is implicated in male infertility and adverse reproductive outcomes. With the publication of many studies regarding the etiologies and contributors to SDF, as well as the effects of SDF, guidelines are necessary to aid clinicians in the application of SDF for male fertility evaluation. Two recent clinical practice guidelines were published by Agarwal et al and Esteves et al. In this article, we have evaluated and compared both guidelines. We have found fairly similar recommendations between the two guidelines and have also highlighted the differences between them. Finally, we have summarized and combined the best practice recommendations from both guidelines. [ABSTRACT FROM AUTHOR]

No increased risk of postpartum major depression (PPMD) was reported in women conceiving through assisted reproductive technologies (ART). However, ART may be associated with a higher risk of parenting difficulties in women with PPMD. In 359 women with a PPMD admitted to a Mother-Baby Unit (MBU), ART-women (4.2%) showed a 5-fold higher rate of parenting difficulties than those with spontaneous pregnancy (73.33% vs. 35.17%, multivariate ORa = 5.09 [1.48–17.48] p = 0.01). Specific support for mother-child relationship should be implemented in ART-women with PPMD. [ABSTRACT FROM AUTHOR]

Introduction. Most men with non-mosaic Klinefelter's syndrome (KS; 47, XXY) have azoospermia, and were until recently considered completely infertile. However, it has been confirmed that some non-mosaic patients had spermatozoa in the ejaculate, although severe oliogasthenoteratosoospermia was present in all of them. Although a high fertilization rate with an intracytoplasmic sperm injection (ICSI) procedure using sperm from a non-mosaic patient and the cumulative pregnancy rate following in vitro fertilization constitute 53%, the incidence of live births after ICSI using sperm of men with non-mosaic KS is very low: 1 in 8 cases. Case report. At the Clinical Centre of Vojvodina's Department of Gynecology and Obstetrics, a successful in vitro fertilization treatment was conducted using the sperm of a man with KS non-mosaic syndrome. Preimplantation genetic testing was performed for the embryo selection, and an euploid embryo was transferred in the subsequent natural cycle. Delivery of male newborn was spontaneous, vaginal, with head presentation, after 40 weeks and 3 days. The newborn's Apgar score was 10/10. His birth weight was 3,950 g, and his length was 55 cm. At 12 months of age, his psychomotor development was assessed as normal on the Brunet-Lézine psychomotor development scale. Conclusion. Due to an increased risk of chromosomal abnormalities (abnormalities of sex or autosomal chromosomes) in embryos from couples with KS males, preimplantation genetic testing is conducted to select a chromosomally normal embryo. This may help achieve pregnancy sooner, decrease the chance of multiple pregnancy and its potential complications, decrease the risk of miscarriage, and reduce the need for invasive prenatal diagnostic procedures and the risks of other complications, as well as the risk of late termination of pregnancy in case of pathological findings of the fetal karyotype using conventional diagnostic procedures. [ABSTRACT FROM AUTHOR]

Heterotopic pregnancy (HP) is a complicated pathological pregnancy, which is rare in natural pregnancy. However, with the development of assisted reproductive technology (ART), the incidence is gradually increasing. Tubal factors and the application of ART are the main factors of HP pathogenesis. It is easy to miss diagnosis or delay diagnosis because of simultaneous intrauterine pregnancy and lack of specificity of symptoms and signs in early stage. The combined application of transvaginal ultrasound and blood hCG value can improve the sensitivity of diagnosis. Therefore, patients with high-risk factors should be in well vigilant, and be diagnosed early, so as to reduce the incidence of adverse obstetric outcomes. Laparoscopic surgery is the main treatment for HP, and other treatments include conservative treatment and drug treatment. Because of the different reproductive needs of patients, the individualized treatment should be adopted to minimize the impact on intrauterine pregnancy and strive for a better pregnancy outcome. If HP can be diagnosed early and treated actively, the prognosis is generally better. [ABSTRACT FROM AUTHOR]

Hydatidiform mole (HM) is a common obstetric disease, which is classified as a gestational trophoblastic disease. HM is characterized by swollen villi. HM can be diagnosed and classified by clinical manifestations and histological examination. However, the complex classification and limitations of etiological knowledge of HM, in addition to the high risk of recurrence, make it difficult to prevent. With the development of sequencing technology, the assisted reproductive technology has been rapidly developed in recent years, especially the pre -implantation genetic testing. These technologies can be applied in the acquisition and evaluation of embryos in vitro. However, the application of assisted reproductive technology in HM patients is still confined due to the limitations of current understanding on HM. There are very limited knowledge on the prevention and reproductive guidance of HM, especially the recurrent HM. The epidemiology, clinical manifestations, histology and the genetic characteristics were reviewed in this article, while the application progress of assisted reproductive technology in HM was also discussed. [ABSTRACT FROM AUTHOR]

The development of assisted reproductive technology (ART) solves the fertility problems of infertile couples, and has a positive effect on human and social progress. However, the medicines commonly used in ART, such as ovary stimulation drugs or progestins, theoretically have the potential risk of inducing female malignant tumors. This article comprehensively reviews 42 clinical studies on the correlation between ART and malignant and/or borderline ovarian tumors reported in English from January 1990 to June 2020, systematically elaborates the risk of ART and fertility drugs on ovary cancer and borderline ovarian tumors. Most of these studies (27/42, 64.3%) showed that ART does not increase the risk of ovary cancer and BOT, but there are also some studies (15/42, 35.7%) affirmed the potential risk of ART on ovary cancer or BOT, especially the researches in the recent 5 years (6/10, 60.0%). The correlation between ART and ovary cancer and BOT need long-term, large sample follow-up and evaluation. [ABSTRACT FROM AUTHOR]

Precision medicine and its advanced technologies have promoted the development of reproductive medicine. The high-throughput sequencing, genome-wide association studies (GWAS), proteomics technology have been successfully used in the etiological diagnosis of infertility, the detection of genetic disease and the pre-implantation genetic testing (PGT) in clinical practice, and the single-celled whole genome amplification (eWGA), biological big data analysis and so on have been also applied in the research of human gamete and early embryo development in recent years. For example, 11 loci and 17 single nucleotide polymorphisms (SNPs) were identified by GWAS, which are strongly correlated with PCOS. When eWGA is applied to PGT, the whole genome information of the egg itself can be deduced by analyzing a single cell obtained from the pre-implantation embryo, so as to reduce the birth with congenital genetic defects and to reduce the iatrogenic risk of assisted reproduction. The artificial intelligence-assisted (AI) method for oocyte or embryo selection during in vitro fertilization-embryo transfer are showing increasing its advantages. This paper reviews the application of precision medicine in assisted reproduction. [ABSTRACT FROM AUTHOR]

According to the pathological etiology of thin endometrium, this paper expounds the pathogenesis and the clinical treatment methods based on a large number of clinical data, case reports and relevant references. The brief principle, clinical efficacy and related side effects of treatment are also included. On the base of the current research progress and new diagnosis and treatment ideas, the possibility of regenerative medicine is filed a discussion. The functional principle and clinical feasibility of bone marrow mesenchymal stem cells (BMSCs) and endometrial stem cells (EDSCs) are mainly discussed, including their clinical feasibility and the limitations, which show us a new hot of further study. This review provides useful reference for clinical treatment of thin endometrium in the future. [ABSTRACT FROM AUTHOR]

Precision medicine and its advanced technologies have promoted the development of reproductive medicine. The high-throughput sequencing, genome-wide association studies (GWAS), proteomics technology have been successfully used in the etiological diagnosis of infertility, the detection of genetic disease and the pre-implantation genetic testing (PGT) in clinical practice, and the single-celled whole genome amplification (eWGA), biological big data analysis and so on have been also applied in the research of human gamete and early embryo development in recent years. For example, 11 loci and 17 single nucleotide polymorphisms (SNPs) were identified by GWAS, which are strongly correlated with PCOS. When eWGA is applied to PGT, the whole genome information of the egg itself can be deduced by analyzing a single cell obtained from the pre-implantation embryo, so as to reduce the birth with congenital genetic defects and to reduce the iatrogenic risk of assisted reproduction. The artificial intelligence-assisted (AI) method for oocyte or embryo selection during in vitro fertilization-embryo transfer are showing increasing its advantages. This paper reviews the application of precision medicine in assisted reproduction. [ABSTRACT FROM AUTHOR]

Heterotopic pregnancy is a kind of pathological pregnancy of the intrauterine pregnancy with simultaneous ectopic pregnancy. The incidence of heterotopic pregnancy is rare in natural condition, about 1/30 000. However, with the application of assisted reproduction, the incidence of complex pregnancy has increased year by year. The intrauterine fetus is precious for those patients with heterotopic pregnancy. How to diagnose and treat the intrauterine fetus accurately is of great significance. However, due to the interference of intrauterine pregnancy, the difficulty of the diagnosis of simultaneous ectopic pregnancy is increased. The misdiagnosis or missed diagnosis of heterotopic pregnancy is common, which seriously threatens the health of mother and child. There is no consensus on the diagnosis and treatment of heterotopic pregnancy. The clinical characteristics, diagnosis and treatment of heterotopic pregnancy, as well as the research progress, were summarized in this review. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of melatonin supplementation during controlled ovarian hyperstimulation for women undergoing assisted reproductive technology. Methods: We searched PubMed, Embase, the Cochrane Library, the CNKI Database, VIP Database, Wanfang Database and the Chinese Biomedicine (CBM) Database for eligible studies published by the end of January 2020. Two independent evaluators screened the randomized controlled trials retrieved the effects of melatonin supplementation during controlled ovarian hyperstimulation in women undergoing assisted reproductive technology. The quality of the included studies was assessed, and the data were extracted for meta-analysis using RevMan 5.3. Results: A total of 6 RCTs involving 767 cycles were included. Among them, 419 cycles were in the melatonin group and 348 cycles in the control group. The meta-analysis showed that the numbers of MⅡ oocytes, high-quality embryos and the E2 levels on hCG day in the melatonin group was significantly higher than those in the control group (P＜0.05). The melatonin supplementation during controlled ovarian hyperstimulation moderately elevated the clinical pregnancy rate, but the difference was not significant (WMD=1.34, P=0.08, 95%CI: 0.96-1.86). However, there were no significant differences in the number of oocytes retrieved and embryos transplanted, fertilization rate and abortion rate between the two groups (P＞0.05). Conclusions: The currently available evidence suggests that melatonin supplementation during controlled ovarian hyperstimulation for women undergoing assisted reproductive technology can improve the numbers of MⅡ oocytes and high-quality embryos, and clinical pregnancy rate. Larger sample size and multicenter RCTs are needed to verify the above conclusions. [ABSTRACT FROM AUTHOR]

Introduction. Extensive use of assisted reproduction has resulted in an increased incidence of triplet pregnancies, which are associated with higher risk of complications in mothers and newborns. Material and Methods. A retrospective study reviewed a total of 85 triplet pregnancies delivered at the Department of Obstetrics and Gynecology, Clinical Center of Vojvodina, Novi Sad, from January 1, 2010 to December 31, 2017. Results. The average maternal age was 32 years and the average body mass index was 30.56 kg/m2. The average gestational age at birth was 32 weeks. One patient (1.18%) had vaginal delivery, while 84 (98.82%) pregnancies were completed by cesarean section. The average blood loss was 1294 ml and there was one postpartum hysterectomy. The most common maternal pregnancy-induced complications were sideropenic anemia (70.58%), hypertensive syndrome (40%) and obstetric cholestasis (35.29%). Preterm premature rupture of membranes was observed in 17 (20%) patients. Prophylactic cerclage was performed in 57 patients (67.05%) and 12 patients (14.11%) received tocolytic therapy. The average birth weight of the first newborn was 1838 g, 1755 g of the second, and 1695 g of the third. Body weight ≤ 1500 g was observed in 61 newborns (24.01%). The mean Apgar score in the first minute was 7, while in the fifth minute it was 8. Respiratory distress syndrome was found in 64 newborns (25.19%). Conclusion. Monitoring and treatment of triplet pregnancies remains a complex task for obstetricians due to the increased incidence of prematurity and perinatal morbidity. [ABSTRACT FROM AUTHOR]

Purpose: Regulation of payment to gamete donors varies substantially across countries. The development of an ethically sustainable governance system of payments in gamete donation demands that the preferences of different stakeholders be heard. This study intends to contribute to improving the understanding of payment to gamete donors by analysing the views of donors and recipients about the preferred form of payment and its associations with their sociodemographic characteristics. Methods: This cross-sectional study included 70 donors and 172 recipients recruited at the Portuguese Public Bank of Gametes (July 2017–June 2018). Participants completed a self-reported questionnaire. Views about the preferred form of payment were collected through a multiple-choice question and an open-ended item. Associations were quantified through χ2 tests; content analysis was conducted with the open-ended answers. Results: Both donors (48.6%) and recipients (40.7%) considered that reimbursement is the preferred form of payment to ensure solidarity-based motivations to donate. This option was followed by compensation for non-financial losses (41.4% of donors; 33.7% of recipients) based on gender equity. Preference for a fixed reward (22.7% of recipients; 8.6% of donors) was less frequent among younger donors and married/living with a partner or employed recipients, being based on the promotion of equality. Conclusion: In the context of the search for cross-border reproductive care and gamete circulation across countries, the findings from this study claim for the need to create solutions for payment to gamete donors that take into account gender equity and are simultaneously sensitive to donor's actual expenses and further health complications. [ABSTRACT FROM AUTHOR]

Previous studies of associations between ASD and conception using assisted reproductive technology (ART) are inconsistent and few studies have examined associations with other infertility treatments or infertility disorders. We examined associations between ASD and maternal/paternal infertility disorders and numerous maternal treatments among 1538 mother-child pairs in the Study to Explore Early Development, a population-based case-control study. ASD was associated with any female infertility diagnosis and several specific diagnoses: blocked tubes, endometriosis, uterine-factor infertility, and polycystic ovarian syndrome. Stratified analyses suggested associations were limited to/much stronger among second or later births. The findings were not explained by sociodemographic factors such as maternal age or education or multiple or preterm birth. ASD was not associated with ART or non-ART infertility treatments. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) has been recognized as a significant cause of suboptimal assisted reproductive outcome. Many of the sperm preparation and manipulation procedures that are necessary in the in vitro environment can result in excessive production of reactive oxygen species (ROS) thereby exposing the gametes and growing embryos to significant oxidative damage. Antioxidants have long been utilized in the management of male subfertility as they can counterbalance the elevated levels of ROS inducing a high state of OS. Few studies have looked into the clinical effectiveness of antioxidants in patients undergoing assisted reproduction. While an overall favorable outcome has been perceived, the specific clinical indication and optimal antioxidant regimen remain unknown. The goal of our review is to explore the sources of ROS in the in vitro environment and provide a clinical scenario-based approach to identify the circumstances where antioxidant supplementation is most beneficial to enhance the outcome of assisted reproduction. [ABSTRACT FROM AUTHOR]

With the extensive use of assisted reproductive technology (ART), it is more and more important to evaluate routinely the uterine cavity by hysteroscopy before the in vitro fertilization-embryo transfer (IVF-ET) cycle, particularly in those patients with repeated implantation failure (RIF). It has been confirmed that hysteroscopy in examination and treatment can improve the clinical outcomes of IVF-ET. The incidence of intrauterine abnormity is about 10% to 15% , such as polyps, submucous myoma, septum, adhesions and chronic endometritis. Vaginal sonography, hysterosalpingography, and saline infusion sonography can be used to evaluate the uterine cavity, while hysteroscopy examination is the golden standard for the diagnosis of intrauterine pathologies. However, the histological examination is the last standard for the diagnosis of endometritis. Hysteroscopy is also an effective tool for the treatment of intrauterine pathologies. The pregnant rate can be significantly increased in those women underwent hysteroscopic surgery, such as transcervical resection of the endometrial polyps (TCRP), transcervical resection of the myoma (TCRM), transcervical resection of the septum (TCRS), and transcervical resection of the intrauterine adhesions (TCRA). The duration after hysteroscopic surgery, for the IVF-ET treatment, depends on the kind of hysteroscopic surgery, ranged from 1 to 3 months. It is true that hysteroscopy plays an important role in the diagnosis and treatment of infertility. However, it is still under debate whether all of infertile women have a routine hysteroscopy before their IVF-ET treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the perinatal outcomes of offspring from IVF/ICSI. Methods： The clinical data and perinatal outcomes of 840 cycles of fresh embryo transfer or frozen-thawed embryo transfer (FET) were retrospectively analyzed in our hospital from January 2012 to December 2013. Results: The birth weight [(2 536.84±417.23)g vs.(3 314.67±466.56)g] and the gestational age[(36.78±1.74)week vs.(39.31±1.45) week] of the twins were significantly lower than singletons (P < 0 .0 5 ). The rates of premature birth (45.66% vs. 3 .7 0 % ), low birth weight(41.32% v s. 2.41% ) and cesarean section(97.26% v s. 81.64% ) in the twins were significantly higher than the singletons(P〈0.05). The birth weight[(3 358.96±458.34)g vs. (3 249.11 ±474.28)g] and the cesarean section (85.97% vs. 74.58% )in the singletons of FET group were significantly higher than those in the fresh embryo transfer group (P < 0 .0 5 ). Conclusions: The twins of ART have more adverse perinatal outcomes than the singletons. The singletons of FET have better outcomes than the singletons of fresh embryo transfer. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynecologic disease with complex pathogenesis. It is very hard to treat. There are at least 25%-35% infertile female with endometriosis. Expectant treatment for infertility patient with endometriosis should not be recommend, and medication should also not be used for increasing the spontaneous pregnancy rate in many guidelines from Europe/USA/China. Surgery and assisted reproductive technologies (ARTs) are important treatment methods, but there are some debates in the strategy and opportune moment of treatment. In this review, we discussed some options on surgery and/or ART for infertility with minimal/mild endometriosis, surgery indication and opportunity in infertility with moderate/severe endometriosis, ovary protection during operation and effect of surgery on ovarian function, dispose after surgery and estimate of pregnancy rate, treatment for recurrent endometriosis with infertility, treatment for infertility with suspected endometriosis, pretreatment with GnRHa before ART in infertility with endometriosis. At last, we present our proposals on the treatment of endometriosis with infertility. [ABSTRACT FROM AUTHOR]

The number and quality of oocyte decline with age. However, the fertility varies significantly even among women of the same age. Many measures have been developed to predict the response to ovarian stimulation and the reproductive potential. Anti-Müllerian hormone (AMH), a glycoprotein secreted by the granulosa cells of small growing follicles, can indirectly reflect the number of follicles in the primordial follicle pool and thus reflect the ovarian reserve. AMH as a practical indicator has been used to predict the ovarian response in IVF cycles, to predict the age of menopause, and to assess the ovarian reserve after iatrogenic injury as well. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). [ABSTRACT FROM AUTHOR]

With the universal two-child policy in China, a considerable part of the rebirth patients are coming into the age of ovarian reserve function decline (DOR) at present. DOR indicates the decreasing reaction to ovarian stimulation, the decreasing quality of oocyte, and the status of "hard to pregnancy and easy to abortion". It is very important to assess accurately and promptly the ovarian reserve of DOR rebirth patients. At present, the treatment strategy for DOR patients includes: ① Assisted reproductive technology (ART) is recommended actively, in which the mild stimulation, minimal stimulation or natural cycles is the increasing popular ART strategy in DOR patients; ②Growth hormones, weak androgens and antioxidants can be added to improve the clinical outcomes of in vitro fertilization (IVF); ③The clinical outcomes could be still unsatisfied for those aged DOR patients even if the donated egg IVF combined with reproductive engineering technology was used. [ABSTRACT FROM AUTHOR]

Objective: To develop the index system, an estimative system for tubal function in patients with tubal infertility, which provide scientific evidence for the prognosis follow-up visit and the postoperative pregnancy guidance. Methods: According to the literature retrieval and our clinical practice, we designed the expert questionnaire. With this expert questionnaire, the index system was developed to evaluate the tubal function after reproductive surgery by the three-round Delphi method and analytic hierarchy method. Results: The authoritative degree after the three-round expert questionnaire was 0.426, with the statistical significance (P＜0.05). The Kendall coefficients of concordance of the first-dimension to the fifth-dimension were 0.625- 0.630, 0.600-0.640, 0.595-0.630, 0.585-0.655 and 0.595-0.650. This index system was constituted with 2 first- dimension, 6 second-dimension, 19 third-dimension, 31 fourth-dimension and 33 fifth-dimension after three- round expert consultation. In all of the indices, the factor of tubal patency in tubal infertile patients after reproductive surgery had the highest weight (0.673). For the weight of tubal patency, it is higher in the bilateral than unilateral tubal patency, the original than recanalized patency, while it is the lowest in the bilateral obstruction. For the weight of tubal morphology, it is higher in the bilateral tubal patency with normal original morphology than others, the morphology and construction of fimbria than the relative location of tube and ovary, and the fimbria atresia than salpingostomy in hydrosalpinx, while it is higher in the peri-tubal adhesion than tubal angulation. For the weight of tubes with abnormal morphology after surgery, it is lower and lower from the fimbria without freedom, the continued abnormal fimbria after salpingostomy to the abnormal mucosa of hydrosalpinx. Conclusions: The index system developed by Delphi method for tubal function evaluation in tubal infertility is reliable and valid, which provide scientific suggestion for the reproductive surgical prognosis and guidance of postoperative pregnancy. [ABSTRACT FROM AUTHOR]

Fallopian tube disease is an important factor of female infertility, including proximal tubal obstruction, distal tubal occlusion, hydrosalpinx, peritubal adhesions, tubal pregnancy and sterilization. Reproductive microsurgery and in-vitro fertilization and embryo transfer (IVF-ET) technology are two treatment modalities, being complementary to each other. Tubal microsurgery should be performed by experienced surgeons in microsurgery and laparoscopy. There are seven fundamental principles of tubal microsurgery as follows: ①to ensure appropriate indications; ②to select correct patients; ③to adopt the least invasive approach; ④to use microsurgery instruments; ⑤to minimize tissue damage; ⑥to ensure precise anatomy reconstruction; ⑦to reduce complication. In this way, the benefit of tubal surgery will be maximized by cautious operation and perfect procedure. [ABSTRACT FROM AUTHOR]

Objective： To compare the clinical outcomes of different strategies of embryo-transfer （ET） on the day 3 of in vitro cultured embryos in IVF treatment cycles. Methods：This is a retrospective study on those ET cycles on the day 3 of in vitro cultured embryos in those patients aged lower than or equal to 35 years in our IVF center from January 2010 to December 2012. All cycles were the first stimulated ovulation induced by long and short programs. The sperm-donor cycles and the genetic diseases cycles were excluded. Ocytes in every cycle were more than or equal to two. The strategies of ET were divided into four groups, based on the embryo number of ET and the embryo score （embryos were scored asⅠ, Ⅱ, Ⅲ, Ⅳ; while Ⅰ and Ⅱ were considered as high-score embryos andⅢandⅣas low-score embryos）. Group A, transfer one high-score embryo;Group B, transfer two high-score embryos; Group C, transfer one high-score embryo and one low-score embryo; and Group D, transfer two low-score embryos. The rates of clinical pregnancy, implantation, twin pregnancy, miscarriage and live birth among 4 groups were compared. Results：There was not significant difference in the miscarriage rates among four groups （8.67%, 10.34%, 13.54%, 20.00%; χ2=4.146, P=0.246）. The rates of clinical pregnancy and live birth per ET cycle in the group B （55.94%, 49.38%） were significantly higher than those in the group A （32.05%、28.63%） and the group C （42.86%, 37.72%）, respectively （P<0.000 1）. The rates of clinical pregnancy and live birth per ET cycle in the group C were significantly higher than those in the group A （P<0.01）. However, the rate of twin pregnancy in the group B （36.31%） was significantly higher than those in the group A （0.67%） and the group C （23.96%） （P<0.01）. Conclusions：The strategy of ET of one high-score embryo combined with one low-score embryo can get acceptable rates of clinical pregnancy and live birth per ET cycle, while it does not increase the rate of twin pregnancy. [ABSTRACT FROM AUTHOR]

The luteal phase defect frequently occurs after the controlled ovarian stimulation and follicular aspiration in assisted reproduction techniques （ARTs）. As a clinical routine, luteal phase support （LPS） is recommended in ART cycles. The LPS treatment with definite curative effect is progesterone alone or progesterone plus hCG. However, hCG is associated with the increased risk of OHSS. Recently, it was showed that the added GnRH agonist in LPS treatment could decrease the OHSS risk, but also improve the outcomes of pregnancy. It is necessary to explore further the formulation of GnRH agonist, the minimal effective dose and the most effective timing and protocol, as well as its exact mechanism. [ABSTRACT FROM AUTHOR]

Objective： To clarify the effect of psychological and physiological factors on IVF/ICSI outcomes by developing a structural equation model. Methods：442 infertility women who met the inclusion criteria were selected randomly as subjects. Psychological questionnaires （STAI, BDI, PSSS and MCMQ） were used to measure psychological status. Data of social demography, basic disease and treatment were also collected. Basic statistical analysis was conducted by SPSS 16.0, and the structural equation model was developed by AMOS20.0. Results：Through the structural equation modeling, we found that the quality of embryos and the psychological states directly influenced the clinical pregnancy outcomes. Age, bFSH, AFC, the number of retrieved oocyte, Gn starting dose, the treatment duration and total dose of Gn indirectly affected the pregnancy outcomes. Conclusions：The crossover effect between psychological and physiological factors were complicated. It is helpful for improving the pregnancy outcomes to remove the negative psychological factors, besides improving biological factors. [ABSTRACT FROM AUTHOR]

The main factors of successful implantation of embryo include the ability to bed, the good receptive endometrium, the interaction of embryo and maternal. Endometrial thickness has been evaluated as a possible predictor of endometrial receptivity. Endometrial thickness in menstrual cycle can reflect the state of endometrial function. Adequate proliferation and secretory changes during the luteal phase is considered to be one of the prerequisites for successful implantation of the embryo. Reports have shown that a thin endometrium is closely associated with lower implantation rates. Furthermore, thin endometrium is an important cause of female infertility. It is important to look for the etiology, active treatment, and improve the endometrium receptivity. Pretreatment to the thin endometrium and increasing endometrial thickness to normal condition will help to improve the rates of pregnancy and live birth. However, the treatments of thin endometrium are not ideal at present. In this paper，we will review the definition，etiology and clinical treatment of thin endometrium. [ABSTRACT FROM AUTHOR]

Objective: To analyze the levels of blood traceelements in those preschool children born from assisted reproductive technology (ART), and to evaluate the developmental status, when compared with those children from natural pregnancy. Methods: Totally, 63 preschool children of ART aged 3 to 6 years (ART group), and 37 children of the same age and from natural pregnancy (control group), from Jiangsu Province were included in this study. Those children with chromosome abnormity, overweight or obesity or other metabolic disorders, had been excluded. Levels of serum zinc, copper, ferrum, calcium, magnesium and lead were analyzed using the BH5100 and BH2100 atomic absorption spectrum instrument and meters. Results: There were not significant differences in body weight, height, bone age, serum biochemistry parameters between two groups. The mean levels of all traceelements in the ART children were in the normal ranges of the same age children. The mean level of zinc in the ART group was slightly lower, and the level of lead higher (P<0.01), than those in the control group. Conclusions: The mean levels of blood traceelements in those preschool children born from ART are within the normal ranges, which suggested the ART safety in the absorption and metabolism of traceelements. It is necessary to study further in the large sample, and to track, whether the levels of zinc and lead are authentically discrepant in those ART children. [ABSTRACT FROM AUTHOR]

In the cycle of frozen-thawed embryo transfer (FET), natural cycle and hormone replacement cycle are the most commonly used for endometrial preparation. There is no disagreement on the necessity of luteal phase support in hormone replacement cycles. However, there are still no consensus on the necessity of luteal phase support in natural cycles, as well as the suitable drugs, dosage form and dose in natural cycles and hormone replacement cycles. There was not a conclusion on the effects of luteal phase support on the outcomes of FET. This review stated the luteal phase support in the cycles of FET, so as to improve clinical application of the luteal phase support. [ABSTRACT FROM AUTHOR]

During a spontaneous menstrual cycle, a preovulatory luteinizing hormone (LH) surge initiates the complex ovulatory process whereby an oocyte is released from the ovarian follicle. As the result of LH surge, the oocytes complete meiosis I and enter meiosis II, the cumulus-oocyte complex separates from the follicle wall, and the process resulting in the release of the oocyte-cumulus complex is started. Human chorionic gonadotrophin (hCG) was usually used as a surrogate LH surge to induce the final ovarian maturation in assisted reproductive technology (ART), because hCG induces the necessary changes through the LH receptor. But the molecular mechanisms of oocyte maturation induced by LH surge in natural cycle are still unclear. The content of LH receptor on granulosa cell increases with the growth of follicles, and reaches a peak before the maturity of follicles, which make the growing follicles to be ready for the response to LH surge. High LH surge acts on GCs by its receptors, stimulating type G protein/adenosine cyclase/cAMP/cAMP-dependent protein kinase (Gs/AC/cAMP/ PKA) pathway to increase intracellular cAMP concentration. The activated transcription factors, including cAMP response element binding protein 1 (CREB1) and cAMP-response element modulator (CREM), causes the activation or inhibition of some gene expressions which related on oocytes maturation and ovulation. All these result in the ovulation and the formation of corpus luteum. [ABSTRACT FROM AUTHOR]

The incidence of monozygotic twining (MZT) is increased in those women treated with assisted reproductive technology (ART). Determining monochorionic or diachorionic twin can be used as a factor for the risk stratification. The perinatal morbidity and mortality of monochorionic diamniotic (MCDA) twin are high. There are several methods of multifetal reduction for MCDA twin with respective merits and demerits. The traditional transvaginal ultrasoundguided puncture and aspiration of embryonic tissue has its demerits. The vessel-occluded techniques have been generally used in the selective reduction for MCDA twin, including the bipolar cord coagulation (BCO) and the radiofrequency ablation (RFA),etc. Premature rupture of membrane (PPROM) and premature delivery are the main complications of selective reduction. However, there is not the standard guideline on the time, method, prognosis and indication of the selective reduction for MCDA twin. It is necessary to do longterm follow-up for those living infants after the multifetal reduction. [ABSTRACT FROM AUTHOR]

Background: Twin pregnancies occur one out of every 800. Due to the increase in maternal age and infertility, the use of assisted reproductive technology (ART) has risen. Thirty five percent of pregnancies solved using ART are twin pregnancies. A RT consists of infertility treatments in which oocytes and sperm are manipulated. The objective of this study was to compare the clinical behavior of premature twins born through ART versus those born after spontaneous conception (SC). Methods: Retrolective cohort study. The data was obtained from the records of preterm twins born between August 2010 and August 2013. Preterm twins were categorized in two groups: the ones conceived using ART versus those conceived through SC. Demographic characteristics and neonatal outcomes were compared. Results: The total was of 398 patients: 208 conceived in consequence of ART and 190 through SC. The primary outcome and neonatal morbidities showed no significant difference, only the incidence of necrotizing enterocolitis and the use of parenteral nutrition showed significant difference. The length of hospital stay between groups was similar. Conclusion: In our population of preterm twins, the mode of conception had no detectable effect on mortality or short term morbidities. [ABSTRACT FROM AUTHOR]

Hypopituitarism is a syndrome caused by corresponding insufficiency of hormones' secretion and results from destroyed anterior pituitary. Amenorrhea, difficulty conceiving, infertility, postpartum no milk occur in hypopituitary patients. The incidence of pregnancy complications is higher, such as abortion, anemia, placental abruption, premature birth and postpartum hemorrhage. So adequate preparation and reasonable use of ART in pre-pregnancy, continuous monitoring of hormone levels and maintaining normal hormone levels in pregnancy and perinatal period can reduce pregnancy complications and improve pregnancy outcomes. This review summarized recent advances about preparation in pregnancy and management in perinatal period of hypopituitarism. [ABSTRACT FROM AUTHOR]

Since its inception, donor conception practices have been a reproductive choice for the infertile. Past and current practices have the potential to cause significant and lifelong harm to the offspring through loss of kinship, heritage, identity, and family health history, and possibly through introducing physical problems. Legislation and regulation in Australia that specifies that the welfare of the child born as a consequence of donor conception is paramount may therefore be in conflict with the outcomes. Altering the paradigm to a child-centric model, however, impinges on reproductive choice and rights of adults involved in the process. With some lobby groups pushing for increased reproductive choice while others emphasise offspring rights there is a dichotomy of interests that society and legislators need to address. Concepts pertaining to a shift toward a child-centric paradigm are discussed. [ABSTRACT FROM AUTHOR]

Background--Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. Methods and Results--This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1-7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1-6.1]; P<0.001), impaired relaxation, and 22 dilated atria (atrial area in controls, 1.46 cm [interquartile range, 1.2-1.5 cm ]; 22 atrial area in ART, 1.6 cm [interquartile range, 1.3-1.8 cm ]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67-83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75-94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45-0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62- 0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. Conclusions--Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated. [ABSTRACT FROM AUTHOR]