Surrogacy: An important pathway to parenthood. A call for international standardization.

This comprehensive review examines the multifaceted landscape of surrogacy, a revolutionary treatment for infertility. The study examines historical origins, shifting trends, medical considerations, psychological implications, legal complexities, international variations, and ethical dilemmas surrounding surrogacy. With the advent of assisted reproductive technology, gestational surrogacy allows intended parents a genetic connection to their child. Medical facets encompass indications for gestational surrogacy, drawing attention to maternal health risks and infertility factors. Evidence indicates that medical outcomes are comparable to conventional pregnancies, suggesting a viable reproductive solution for intended parents. Due to the complex nature of surrogacy psychological and emotional vulnerability is inevitable; yet studies underscore positive psychological well-being and satisfaction among gestational carriers (GCs), intended parents (IPs) and children. Surrogacy also has many religious dimensions, as each religion has its own perspective on the distinctive process of creating life and its outcomes, such as, the determination of the child's mother according to their beliefs. Legal considerations emerge as a fundamental aspect, with differing regulations globally. The review emphasizes the significance of comprehensive agreements to safeguard the rights and responsibilities of surrogates and IPs. The unique surrogacy laws in Israel serve as a noteworthy example, reflecting a progressive approach that provides a promising template to establish crucial international guidelines on surrogacy. The absence of international consensus necessitates attention from the global community to address key concerns, including the well-being of GCs, legal recognition for IPs, and the child's best interests, with the goal of establishing a universal standard of care in the field.

Prevention of Pregnancy Loss: Combining Progestogen Treatment and Psychological Support.

Pregnancy loss can be defined as a loss before either 20 or 24 weeks of gestation (based on the first day of the last menstrual period) or the loss of an embryo or fetus less than 400 g in weight if the gestation age is unknown. Approximately 23 million pregnancy losses occur worldwide every year, equating to 15-20% of all clinically recognized pregnancies. A pregnancy loss is usually associated with physical consequences, such as early pregnancy bleeding ranging in severity from spotting to hemorrhage. However, it can also be associated with profound psychological distress, which can be felt by both partners and may include feelings of denial, shock, anxiety, depression, post-traumatic stress disorder, and suicide. Progesterone plays a key part in the maintenance of a pregnancy, and progesterone supplementation has been assessed as a preventative measure in patients at increased risk of experiencing a pregnancy loss. The primary objective of this piece is to assess the evidence for various progestogen formulations in the treatment of threatened and recurrent pregnancy loss, postulating that an optimal treatment plan would preferably include a validated psychological support tool as an adjunct to appropriate pharmacological treatment.

Increased Live Birth Rate with Dydrogesterone among Patients with Recurrent Pregnancy Loss Regardless of Other Treatments.

BACKGROUND: Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies. Several treatment options are available, including progesterone, which is one of the few treatments that improve live birth rates in RPL patients. OBJECTIVE: To compare the live birth rates, medical and obstetric characteristics, and RPL evaluation results of women with and without progesterone treatment. These women attended the RPL clinic at Soroka University Medical Center. METHODS: A retrospective cohort study based on 866 patients was conducted. The patients were divided into two groups and examined: the dydrogesterone treatment group consisting of 509 women and a group of 357 patients who did not receive the treatment. All the patients had a subsequent (index) pregnancy. RESULTS: The two groups were not statistically different in terms of their demographic and clinical characteristics or evaluation results. In a univariate analysis, no statistically significant differences were found between the groups in terms of live birth rates (80.6% vs. 84%; p-value = 0.209). In a multivariate logistic analysis adjusted for maternal age, the ratio of pregnancy losses to the number of pregnancies, other administered treatments, antiphospholipid syndrome, and body mass index, dydrogesterone treatment was found to be independently associated with a higher rate of live births than the control group (adjusted OR = 1.592; CI 95% 1.051-2.413; p-value = 0.028). CONCLUSIONS: Progesterone treatment is associated with an increased live birth rate in RPL patients. Studies with larger sample sizes are recommended to strengthen these results.

A proposed prognostic prediction tool for a live birth among women with recurrent pregnancy loss.

PURPOSE: To develop a prognostic tool to predict the live birth rate in cases of repeated pregnancy losses. STUDY DESIGN: A retrospective cohort study including patients treated in the dedicated RPL clinic between 2000 and 2015. Background data was collected in the primary visit via questionnaires and medical records. The recurrent pregnancy loss workup includes a genetic testing, endocrine testing, and anatomic abnormalities as well as thrombophilia.The prognostic tool took into account the unique contribution of the different risk factors, including maternal age, number of pregnancy losses, primary vs. secondary RPL and positive RPL workup. RESULTS: A total of 675 women were included in the study. The live birth rate was 72% (484). It was significantly associated with age (p=.002), number of previous pregnancy losses (p=.016), primary and secondary RPL and positive RPL workup. Each variable was assigned points according to the odds ratio found in the logistic regression to create two prediction models, before and after the RPL workup. Both models show a rise in the live birth rate as the score increases. CONCLUSIONS: We constructed a proposed innovative prognostic tool to predict the chance of a live birth on the consecutive pregnancy following the visit to the RPL clinic. Locating, identifying and improving risk assessment can enable the provision of up-to-date information to couples and the treating staff. This knowledge will reduce stress among the patients and will allow the staff to constructed custom intervention programs.

Exposure to General Anesthesia May Contribute to the Association between Cesarean Delivery and Autism Spectrum Disorder.

Cesarean section (CS) has been consistently associated with susceptibility to autism spectrum disorder (ASD), however, the underlying mechanism for this association remains vague. Here, we studied various pre-peri-and-neonatal factors among 347 children with ASD, 117 children with other developmental delays (DD), and 2226 age, sex and ethnicity matched controls. We found that CS is significantly associated with an increased risk of ASD but not DD (p = 0.019 and p = 0.540 respectively). Furthermore, we show that only CS performed with general anesthesia (GA) elevated the risk of ASD with no significant difference between indicated and non-indicated surgeries (aOR = 1.537; 95% CI 1.026-2.302, and aOR = 1.692; 95% CI 1.057-2.709, pdiff = 0.865). We therefore suggest that exposure to GA during CS may explain the association between CS and ASD.

A rare cause of postpartum acute hyponatremia.

A previously healthy 24-year-old female underwent an emergent caesarean section without a major bleeding described. During the first post-operative days (POD) she complained of fatigue, headache and a failure to lactate with no specific and conclusive findings on head CT. On the following days, fever rose with a suspicion of an obstetric surgery-related infection, again with no evidence to support the diagnosis. On POD5 a new-onset hyponatremia was documented. The urine analysis suggested SIADH, and following a treatment failure, further investigation was performed and demonstrated both central hypothyroidism and adrenal insufficiency. The patient was immediately treated with hydrocortisone followed by levothyroxine with a rapid resolution of symptoms and hyponatremia. Further laboratory investigation demonstrated anterior hypopituitarism. The main differential diagnosis was Sheehan's syndrome vs lymphocytic hypophysitis. Brain MRI was performed as soon as it was available and findings consistent with Sheehan's syndrome confirmed the diagnosis. Lifelong hormonal replacement therapy was initiated. Further complaints on polyuria and polydipsia have led to a water deprivation testing and the diagnosis of partial central insipidus and appropriate treatment with DDAVP. Learning points: Sheehan's syndrome can occur, though rarely, without an obvious major post-partum hemorrhage. The syndrome may resemble lymphocytic hypophysitis clinically and imaging studies may be crucial in order to differentiate both conditions. Hypopituitarism presentation may be variable and depends on the specific hormone deficit. Euvolemic hyponatremia workup must include thyroid function test and 08:00 AM cortisol levels.

Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions.

Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

Prevalence and trends of pelvic floor disorders in late pregnancy and after delivery in a cohort of Israeli women using the PFDI-20.

OBJECTIVE: To investigate the prevalence of pelvic floor disorders (PFD) in a cohort of Israeli women at late pregnancy and three months postpartum, to define changes in PFD rates and to evaluate various obstetrical factors that may correlate with these changes. METHODS: A prospective longitudinal cohort study was conducted between March and July 2014. The PFDI-20 questionnaire (validated in the Hebrew language) was used to evaluate pelvic floor distress symptoms 24h and 3 months after delivery (representing the third trimester and post-partum period, respectively). Patients with a preterm delivery (<36 completed weeks of gestation), delivery of a stillbirth, non-fluency in Hebrew and patients with inability to complete the questionnaire due to a communication problem were excluded from the study. In addition to the PFDI results demographic and clinical data were collected from the patients' medical records. Routine statistical methods were used to interpret the results. RESULTS: During the study period 117 women answered the first questionnaire and only 37 had filled the second questionnaire. The most prevalent item group reported in the third trimester was the urinary distress symptoms. Urinary frequency was the most common with 65% of patients reporting this symptom. At the post-partum period the most prevalent item group reported was the colorectal and anal distress with 31.5% of patients reporting increased straining efforts. There was a mixed trend in the changes noted between the two questionnaires. While some items improved in the puerperium as compared with late pregnancy others have worsened. In a multivariable analysis the only statistically significant finding was that at the post-partum follow-up, stress urinary incontinence was significantly associated with spontaneous perineal tears at delivery. Other obstetrical parameters including episiotomy and birth weight were not found to be significantly associated with any of the PFD items. CONCLUSION: We have demonstrated that PFD is prevalent both in late pregnancy and in the puerperium. There are mixed trends of spontaneous recovery following childbirth. A significant association between perineal tears and SUI 3 months after delivery was noted.

Bibliometrics: tracking research impact by selecting the appropriate metrics.

Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist's profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact.

Index pregnancy versus post-index pregnancy in patients with recurrent pregnancy loss.

OBJECTIVE: To compare pregnancy outcomes of two consecutive pregnancies in a cohort of women with recurrent pregnancy loss (RPL), in order to determine the long-term prognosis of women with RPL managed in a dedicated RPL clinic. METHODS: A retrospective cohort study including 262 patients with two or more consecutive pregnancy losses followed by two subsequent pregnancies--index pregnancy (IP) and post-index pregnancy (PIP). All patients were evaluated and treated in the RPL clinic in the Soroka University Medical Center. RESULTS: Comparing IP with PIP, no significant difference in perinatal outcome was observed. The perinatal outcome remained encouraging with approximately 73% birth rate (73.7% versus 72.5%; p=0.83). Only 11% of the women with RPL continued to experience pregnancy losses for two subsequent pregnancies. In a multivariate logistic regression analysis, number of miscarriages pre-Index was the only factor independently associated with birth in the PIP. CONCLUSION: There is no significant difference between IP and PIP regarding perinatal outcome. Appropriate management in the RPL clinic conferred a significant beneficial effect on long-term pregnancy outcome of a cohort of women with RPL.

Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat.

Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet not much is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n = 4/group) at the time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations led to identification of indolethylamine N-methyltransferase, tissue factor pathway inhibitor-2, and ephrin type-B receptor 6, not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis as compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity.

Third-trimester abnormal uterine artery Doppler findings are associated with adverse pregnancy outcomes.

OBJECTIVES: To evaluate the association between third-trimester abnormal uterine artery Doppler findings and pregnancy outcomes. METHODS: A prospective study was designed, including 198 consecutive singleton pregnancies between 27 and 41 weeks' gestation. In the study population, 144 had normal uterine artery Doppler waveforms, 37 had unilateral pathologic waveforms, and 17 had bilateral pathologic waveforms. Eighty patients had intrauterine growth restriction (IUGR), preeclampsia toxemia, or both, and 118 had no complications and served as a control group. The uterine artery Doppler waveform was considered abnormal when a notch or pulsatility index above the 90th percentile was noted. RESULTS: In patients with bilateral pathologic uterine artery Doppler waveforms, the rates of cesarean delivery, small-for-gestational-age (SGA) neonates, preterm delivery, and low Apgar scores were increased compared to patients with normal or pathologic unilateral waveforms (P = .009; P > .001; P = .007; P > .001, respectively). The incidence rates for SGA neonates, cesarean delivery, and preterm delivery were significantly higher among patients without IUGR or preeclampsia toxemia when associated with pathologic bilateral waveforms in comparison to normal waveforms (P = .01 for all). A bilateral pathologic waveform was found to be an independent risk factor for cesarean delivery and SGA neonates. The incidence rates for SGA neonates and preterm delivery were significantly higher among patients with IUGR and/or preeclampsia toxemia when associated with bilateral abnormalities in comparison to normal waveforms (P = .01 for both). CONCLUSIONS: Third-trimester abnormal uterine artery Doppler findings are associated with worse perinatal outcomes among patients both with and without pregnancy complications.

Effect of interpregnancy interval on outcomes of pregnancy after recurrent pregnancy loss.

OBJECTIVE: To examine the effect of interpregnancy interval (IPI) on outcomes of pregnancy after recurrent pregnancy loss (RPL). METHODS: A retrospective cohort study including 325 patients treated at a RPL clinic, with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy, of whom 163 had IPI ≤ 6 months, and 212 had IPI > 6 months. RESULTS: Pregnancy loss rate in the index pregnancy was positively associated with increased IPI (18.6% in women with IPI ≤ 6 months, and 29.7% in women with IPI > 6 months; p = 0.029). In a multivariable logistic analysis, excluding women with fertility problems, and adjusting for maternal age and ethnicity, the OR for pregnancy loss rate for IPI longer than 6 months compared to shorter IPI was 1.76 (95%CI: 0.96-3.22, p = 0.067). CONCLUSIONS: Our results suggest that IPI shorter than 6 months, in women with no fertility problems, is associated with lower rate of subsequent miscarriage. Further studies are needed to substantiate this finding.

Tomato extract and the carotenoids lycopene and lutein improve endothelial function and attenuate inflammatory NF-κB signaling in endothelial cells.

OBJECTIVES: In our previous research the antihypertensive properties of lycopene-containing tomato oleoresin have been revealed. The present study was aimed to assess if oleoresin interferes in the inflammatory signalling in endothelial cells, imitating reduction of inflammatory processes in the vessel wall and in this way to propose the mechanism for the reduction of blood pressure by oleoresin. METHODS AND RESULTS: A wide number of functional and inflammatory markers were investigated in two cultured endothelial cell models [EA.hy926 and human umbilical vein endothelial cell (HUVEC)], exposed to oleoresin and carotenoids lycopene and lutein. All the carotenoids significantly improved basic endothelial function as measured by increased nitric oxide and decreased endothelin (ET-1) release. They were effective in attenuation of inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling: decrease of tumour necrosis factor-alpha (TNF-α)-induced leukocytes adhesion, expression of adhesion molecules inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and nuclear translocation of NF-κB components as well as some revert of inhibitor of kappa B (IκB) ubiquitination. In addition, the carotenoids were able to inhibit NF-κB activation in transfected endothelial cells. When combined with lutein, oleoresin exerted synergistic effect on preclusion of leukocytes adhesion. CONCLUSIONS: Prevention of over-expression of adhesion molecules through inhibition of NF-κB signalling may be one of the main mechanisms driving carotenoids to attenuate inflammatory leukocyte adhesion to endothelium. This is the first profound study on the mechanisms involved in the positive action of natural tomato products in endothelial cells.

Anxiety and deterioration of quality of life factors associated with recurrent miscarriage in an observational study.

OBJECTIVES: To examine the relationship of anxiety and quality of life and sleep variables to recurrent miscarriages (RMs) in patients during two stages of their treatment in an RM-dedicated clinic ­ before and after the evaluation ­ and determine what factors could aggravate anxiety and worsen global well-being outcomes. STUDY DESIGN: Thirty-nine women who had experienced two or more RMs were measured before and after their evaluation and investigation in the RM clinic. A battery of questionnaires including the STAI scale and various instruments were administered to record anxiety, mental, and physical components of quality of life and sleep quality. Several statistical tests including canonical correlation were performed. RESULTS: All the patients revealed a mild to moderate level of anxiety, low numbers of physical and mental health but reasonably normal values of the global quality of sleep. The evaluation in the RM clinic and investigation for possible causes accounting for RM did not significantly change anxiety levels. The children-to-pregnancies ratio introduced into the analysis proved to correlate significantly with the sleep quality and mental health. Summarized anxiety in a given RM woman could be predicted based on the set of the variables, characterizing the woman's reproductive status and her psychological health. CONCLUSIONS: This study establishes anxiety as a common response in RM patients, and suggests factors that predict it. Knowing these factors may help clinicians to identify more accurately those RM patients who would be prone to a high level of anxiety and therefore need more attention and reassurance.

Two vs. three or more primary recurrent pregnancy losses--are there any differences in epidemiologic characteristics and index pregnancy outcome?

OBJECTIVE: To compare obstetric characteristics and pregnancy outcomes of patients following two vs. three or more primary recurrent pregnancy losses (RPL). STUDY DESIGN: A retrospective cohort study including 168 patients with primary RPL followed by subsequent (index) pregnancy, 124 patients with three or more consecutive RPL, and 60 patients with two consecutive RPL was performed. All patients were evaluated and treated in the RPL Clinic in the Soroka University Medical Center. RESULTS: Obstetric characteristics of the study groups were similar. Women with three or more RPL compared to women with two RPL had a higher rate of abnormal thyroid stimulating hormone (TSH) levels (16.3 vs. 2.6%; P=0.033), higher rates of spontaneous pregnancy (91.7 vs. 77.4%; P<0.05), and higher rates of Clexane treatment (40.3% vs. 18.6%; P=0.016). In the index pregnancy, live birth rate was not statistically different between the two groups (81.1% in the two-RPL groups vs. 70.6% in the three-RPL group) nor was neonatal mortality. CONCLUSIONS: Patients with two RPL and three RPL had very similar obstetric characteristics and evaluation test results. Differences in index pregnancy outcomes were not statistically significant. Therefore, evaluation in primary RPL is recommended after two RPL.

Primary vs. secondary recurrent pregnancy loss--epidemiological characteristics, etiology, and next pregnancy outcome.

OBJECTIVE: To compare epidemiological and obstetric characteristics, etiology and next pregnancy outcomes of women with primary vs. secondary recurrent pregnancy loss (RPL). STUDY DESIGN: A retrospective cohort study, including 420 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy, of whom 162 were primary RPL women and 258 were secondary RPL women. All patients were evaluated and treated in the RPL clinic at the Soroka University Medical Center. RESULTS: Live birth rate in the index pregnancy was not statistically different between primary and secondary RPL women (75.9 and 70.9%, respectively). The only significant difference in the etiology evaluation was in abnormal prolactin levels (14.1% of the primary and 1.4% of the secondary RPL group). Women with primary RPL had, at the index pregnancy, significantly higher rates of preterm delivery, fetal growth restriction, and gestational diabetes mellitus. In a multivariable logistic regression analysis, primary RPL adjusted for maternal age and gravidity, was an independent risk factor for preterm delivery compared with secondary RPL [adjusted OR 2.62, CI (95%) 1.30-5.26]. CONCLUSIONS: The prognosis of the two groups was similar regarding live birth rate at the index pregnancy; however, women with primary RPL were more prone to adverse obstetric and neonatal outcomes.