Leiomyoma: genetics, assisted reproduction, pregnancy and therapeutic advances

Purpose

Uterine leiomyomas are common, benign, reproductive tract tumors affecting a majority of reproductive aged women. They are associated with gynecologic morbidity and detrimentally affect reproductive potential. The etiology of leiomyomas is poorly understood and their diagnosis prior to treatment with Assisted Reproductive Technologies (ART) represents a management dilemma. The purpose of this paper is to review known genetic and molecular contributions to the etiologies of leiomyomas, describe their impact on ART outcomes and reproductive potential, and review alternative therapies and future directions in management.

Methods

A critical review of the literature pertaining to genetic component of uterine leiomyomas, their impact on ART and pregnancy and leiomyoma therapeutics was performed.

Results

Uterine leiomyomas are characterized by complex molecular mechanisms. Their location and size determines their potential detriment to ART and reproductive function and novel therapeutic modalities are being developed.

Conclusion

The high prevalence of uterine leiomyomas and their potential detrimental influence on ART and reproductive function warrants continued well-designed studies to ascertain their etiology, optimal treatment and novel less morbid therapies.     

Network support and parenting in mothers and fathers who conceived spontaneously or through assisted reproduction

Background: Little is known about the contribution of other significant relationships beyond the partnership for parental adjustment and care in parents who conceived through Assisted Reproductive Technologies (ART). Objective: This study examined the role of perceived network support on parenting stress and investment in the child in parents who conceived spontaneously or through ART, during their transition to parenthood. Methods: Thirty‐five couples who conceived through ART and 31 couples who conceived spontaneously completed self‐report questionnaires regarding perceived emotional and instrumental support from their social network members (i.e. nuclear and extended family members and friends) during pregnancy (twenty‐fourth week) and regarding parenting stress and investment in the child four months after the partum. Results: Regardless of method‐of‐conception, instrumental support from the nuclear family was positively associated with maternal investment in the child and emotional and instrumental support from the extended family were positively associated with paternal stress while support from friends was negatively associated with it. Conclusion: Results suggest that parents who conceive through ART and spontaneously are alike in that their adjustment to parenthood and the quality of the care they provide to their children depends on perceived support from nuclear and extended family and friends.     

Growing families in a shrinking world: legal and ethical challenges in cross-border surrogacy

Crossing national borders to have children is a rapidly growing phenomenon, fuelled by restrictions on access and technologies in some countries and for some patients, by high costs in others, and all generating a burgeoning multibillion dollar international industry. Cross-border gestational surrogacy is one form of family building that challenges legal, policy and ethical norms between countries and puts both intended parents and gestational surrogates at risk, and can leave the offspring of these arrangements vulnerable in a variety of ways, including parent–child, immigration and citizenship status. The widely varying political, religious and legal views amongst countries make line drawing and rule making challenging. This article reviews recent court decisions about and explores the legal dimensions of cross-border surrogacy.Crossing national borders to have children is a rapidly growing phenomenon, fuelled by restrictions on access and technologies in some countries and for some patients, by high costs in others, and all generating a burgeoning multibillion dollar international industry. Cross-border gestational surrogacy is one form of family building that challenges legal, policy and ethical norms between countries and puts both intended parents and gestational surrogates at risk, and can leave the offspring of these arrangements vulnerable in a variety of ways, including parent–child, immigration and citizenship status. The widely varying political, religious and legal views amongst countries make line drawing and rule making challenging. This article reviews recent court decisions about and explores the legal dimensions of cross-border surrogacy.VIDEO LINK: http://sms.cam.ac.uk/media/1401580     

Anger in women treated with assisted reproductive technology (ART): effects on mother and newborn

Objective: To assess anger, as well as other negative emotions, in women who underwent assisted reproductive technology (ART) respect to women who conceived naturally, and explore the effect of anger on neonatal outcomes.

Methods: We recorded personal and obstetric history of the patients, neonatal weight, Apgar score, obstetric and neonatal complications. We performed Structural Clinical Interview for DSM-SCID I and II in order to assess the DSM IV axis I and axis II, State-Trait Anger Expression Inventory 2 (STAXI-2), the Self-rating Depression Scale (SDS) and Self-rating Anxiety scale (SAS).

Results: On the STAXI-2 scale, the ART group scored higher than the natural conception group on measures of general tendency and personality disposition to get angry. Moreover, the ART group women showed quite low levels of tolerance to negative environmental feedback. Our results further suggest that trait anger provides the most meaningful contribution as predictor of weight at birth. No significant differences were found for anxiety and depression between the two groups.

Conclusions: Our study highlights the important role of anger during pregnancy, and suggests the need for further studies on both biochemical and behavioural patterns in larger samples of women who became pregnant by ART.     

Use of assisted reproductive technologies and anesthesia in a patient with primary pulmonary hypertension

OBJECTIVE: To report the use of assisted reproductive technologies (ART) in a patient with primary pulmonary hypertension. DESIGN: Case report. SETTING: University medical center. PATIENT(S): A 28-year-old nulliparous woman with primary pulmonary hypertension (PPH) treated with continuous intravenous epoprostenol. INTERVENTION(S): Ovarian stimulation, egg retrieval, general anesthesia, and pregnancy by surrogate carrier. MAIN OUTCOME MEASURE(S): Successful ART cycle(s) in patient with PPH and successful gestational carrier pregnancy. RESULT(S): Successful pregnancy by surrogate gestational carrier. CONCLUSION(S): Assisted reproductive technologies and a surrogate gestational carrier were a successful reproductive option for a patient with primary pulmonary hypertension. Ovarian stimulation, oocyte retrieval, and general anesthesia are not without risk but were well tolerated in this case. Multidisciplinary involvement in the planning and administration of such procedures is necessary for optimal outcomes in these patients.     

子宫内膜非典型增生18例保守治疗结局分析

目的探讨孕激素治疗子宫内膜非典型增生的结局及适宜的辅助生育策略。方法回顾性分析2002年1月～2007年4月18例不孕合并子宫内膜非典型增生的患者应用大剂量孕激素保守治疗的结果及妊娠结局。结果①14例患者在应用大剂量孕激素治疗3～36个月后病灶消退，4例病灶持续存在；②3例患者在停止治疗5～15个月后发展为子宫内膜癌。内膜非典型增生病变的再现率为33．3％；③8例患者接受了辅助生育治疗．5例分别经CC＋HMG促排卵治疗3～6周期无优势卵泡发育．1例在第6个促排卵周期获宫内单胎妊娠。4例（包括1例CC＋HMG促排卵未孕者）患者接受了5个周期IVF助孕，1例输卵管妊娠。1例自然流产。另2例冻存胚胎等待移植。结论多数子宫内膜非典型增生的患者对大剂量孕激素治疗有效。对这类患者．一旦内膜病变消退，应积极助孕．可以适当放宽IVF—ET指征。     

Post-neonatal health and development of children born after assisted reproduction: a systematic review of controlled studies

Long-term follow-up studies on the health and the development of children conceived by assisted reproduction (ART) are mandatory to assess the safety of ART. Meanwhile, different aspects of health of these children have been studied. To put these results together, we performed a systematic review of these publications. A Pubmed search and a hand-search of the abstract books from the annual meeting of the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine were performed for controlled studies on the developmental outcome of children after ART, which include a matching for plurality of gestation. Regarding general health, growth, mental and psychomotor development IVF children do not differ from spontaneously conceived (SC) children. An increased need for surgical interventions may be due to an increase in the malformation rate. However, a lower birth weight and lower gestational age compared to matched controls may contribute to some health problems observed. The increased risk of neurological problems found in some large registry-based studies can partly be explained by the higher frequency of twins born, by low birth weight, and by low gestational age also found in singletons. But an effect of IVF, the parents' infertility or other factors not adjusted for in the studies cannot be excluded. In addition to this reporting bias caused by concerned parents cannot be excluded, either. To conclude, children born after assisted reproductive techniques are generally healthy and are developmentally similar to children born after SC. However, low birth weight and prematurity contributes to health care problems. An increase of neurological problems by IVF cannot be excluded. Further prospective studies on the neurological outcome are needed.     

The association between poor ovarian response and thrombophilia in assisted reproduction

Objective

To investigate the association between thrombophilic risk factors and poor ovarian response in an assisted reproductive technologies (ART) setting.

Study design

This is a preliminary prospective cohort study in a university affiliated reproductive medicine unit. Eighty-nine infertile women undergoing IVF-ET treatment were recruited. Following IVF-ET treatment, the 28 women that had ≤3 oocytes on retrieval were the study group, and the 61women that had ≥ 4 oocytes on retrieval were the control group. All women underwent ovarian reserve testing and thrombophilia work-up prior to treatment.

Results

Patients’ characteristics, except for chronological age, were similar between the two groups. Women in the study group had clear manifestations of low ovarian reserve, evident by ovarian reserve testing, controlled ovarian hyper-stimulation and IVF-ET treatment results, as compared to the control group. The incidence of all thrombophilias tested was similar between the study and control group. Moreover, the incidence of any single or combined thrombophilia was also similar between the two groups. Logistic regression model analysis and Pearson correlation tests did not show significant correlation between number of oocytes retrieved and thrombophilia. Furthermore, basal ovarian reserve tests did not differ between women with and without thrombophilia. When only the 48 women ≤ 35 years of were analyzed, the five women in the study group had significantly higher incidence of a single as well as combined thrombophilia as compared to the 43 controls.

Conclusions

Thrombophilic risk factors have no correlation with poor ovarian response in the general infertile population undergoing ART. Whether premature low ovarian reserve is linked to thrombophilia remains to be established.     

Reproductive healthcare systems should include accessible infertility diagnosis and treatment: An important challenge for resource-poor countries

Infertility is a central issue in the lives of many couples who suffer from it. In resource-poor countries the problem of childlessness is even more pronounced compared with Western societies owing to different sociocultural circumstances. It often leads to severe psychological, social, and economic suffering, and access to infertility treatment is often limited to certain procedures and certain costumers. The issue of infertility in resource-poor countries is underestimated and neglected, not only by local governments but also by the international nonprofit organizations. Simplification of the diagnostic and therapeutic procedures, minimizing the complication rate, and incorporating fertility centers into existing reproductive healthcare programs are essential measures to take in resource-poor countries if infertility treatment is to be accessible for a large part of the population. For reasons of social justice, a search for strategies to implement simplified methods of infertility diagnosis and treatment in resource-poor countries is urgently warranted.     

Role of religion,spirituality, and faith in assisted reproduction

Purpose: The purpose of this study is to evaluate the impact of the patient’s faith, religion, and spirituality on the outcomes of intracytoplasmic sperm injection (ICSI) cycles.

Materials and methods: Eight hundred and seventy-seven patients received a questionnaire containing information on faith, religiosity, and spirituality and the results of the questionnaires were correlated with ICSI outcomes. Patients stated to be Catholic (n?=?476), spiritists (n?=?93), Evangelical (n?=?118), and other religion (n?=?32), and 78 did not identify with any religious group.

Results: A significant increase in fertilization, high-quality embryos, and pregnancy rate was found among Spiritists and Evangelicals. Patients who included the infertility diagnosis and treatment in their prayers showed an increased pregnancy rate, and those who reported their faith to be affected by the infertility diagnosis presented a decreased high-quality embryos rate. The high-quality embryos rate was increased among patients who answered that their faith contributed to their decision to undergo infertility treatment. The cycle’s cancelation was negatively correlated with the frequency of religious meetings, and the frequency of prayers was positively correlated with the response to ovarian stimulation. Finally, belief in treatment success positively influenced the embryo quality.

Conclusion: The findings suggest that spirituality plays a role in adjusting the psychological aspects of an infertile patient.     

Hormonal medication in medically assisted reproduction: a systematic review of assessments from patients

Several hormonal fertility medications have comparable effectiveness. A literature review was conducted into patients’ assessments regarding seven medication characteristics including ‘side effects’ and ‘ease of use’. Medline, CINAHL and PsycINFO were searched for female fertility patients’ written assessments of a hormonal medication. The tools used were appraised and common (i.e. ≥10%) unpleasant consequences were distinguished from rare ones. The 35 eligible studies did not rely on valid and reliable tools and did not provide patient assessments regarding all seven medication characteristics for any of the globally used medications. Evidence on medications for oocyte triggering was absent and for induction of pituitary quiescence it was scarce. Regarding medications for ovarian stimulation and luteal support, evidence on general side effects (mostly headache), local side effects (mostly pain), ‘interference with home life’ and ‘impact on psychological wellbeing’ was found. Evidence on ‘ease of use’ and ‘required education’ was only identified for medication for ovarian stimulation. Evidence on ‘interference with work life’ and ‘compliance worry’ was absent. This review calls for randomized controlled trials questioning patients with valid and reliable tools. In the meantime, this review's summary of the best available evidence can be integrated in decision aids facilitating personalized and informed medication choices.     

Comparison of embryo transfer strategies and assisted reproduction outcome in Slovenian and cross-border patients

A reduction in the number of embryos transferred is the most important step in decreasing multiple gestation rates after medically assisted reproduction. Slovenia has implemented insurance company regulations that regulate single-embryo transfer in selected good-prognosis couples. The aim of the present study was to evaluate its effects on the Slovenian population compared with cross-border patients, who are not affected by the insurance company policy. Ultimately, 2403 couples undergoing IVF or intracytoplasmic sperm injection were included in the retrospective analysis. Patients were classified according to their origin. The decision about the number of embryos transferred and the treatment success were evaluated. The implementation of the policy favouring single-embryo transfer resulted in a significant decrease in the twin birth rate in Slovenian patients (24.4% before policy versus 6.7% after policy implementation, P < 0.001). Although in cross-border patients twin birth rates have declined through the study period, they remained significantly higher compared with Slovenian patients (23.1% versus 6.7%, P < 0.001). The data demonstrate that insurance company policies favouring single-embryo transfer are an effective tool in decreasing multiple gestation rates. Similar mechanisms should be implemented in the cross-border patient population.A reduction in the number of embryos for transfer is the most important step in decreasing multiple gestation rates after medically assisted reproduction. Slovenia has implemented insurance company regulations that regulate single-embryo transfer in selected good-prognosis couples. This means that in patients with female partner younger than 36 years, undergoing their first or second treatment attempt, a single top-quality should be transferred in order for national insurance company to reimburse six IVF/intracytoplasmic sperm injection (ICSI) cycles. The aim of the present study was to evaluate the effect of this regulation on the Slovenian patient population compared with cross-border patients, who are not affected by insurance company policy. Ultimately, 2403 couples undergoing IVF or ICSI procedure were included in the analysis. Patients were classified according to their origin. The decision about the number of embryos for transfer and treatment success was evaluated. The implementation of the policy favouring single-embryo transfer resulted in a significant decrease in the twin birth rate in Slovenian patients (24.4% before versus 6.7% after policy implementation). Although in cross-border patients, twin birth rates have declined through the study period, they remained significantly higher compared with Slovenian patients (23.1% versus 6.7%). Our data demonstrate that insurance company policies favouring single-embryo transfer are an effective tool in decreasing multiple gestation rates. Similar mechanisms should be implemented in the cross-border patient population.     

Follicle aspiration, sperm injection, and assisted rupture (FASIAR): a simple new assisted reproductive technique

Objective: To describe the first successful application of a new fertility-enhancing technique.

Design: Case report.

Setting: Academic fertility program.

Patient(s): A 36-year-old nulligravid woman undergoing inseminations with frozen-thawed donor sperm.

Intervention(s): Ovarian superovulation, follicle aspiration, sperm injection, and assisted follicular rupture.

Main Outcome Measure(s): Assessment of feasibility of technique and pregnancy outcome.

Result(s): After failing to conceive during 16 cycles of IUI, the patient successfully achieved an ongoing pregnancy during the second follicle aspiration, sperm injection, and assisted rupture (FASIAR) attempt.

Conclusion(s): Follicle aspiration, sperm injection, and assisted rupture combines the concepts of superovulation, IUI, and peritoneal oocyte and sperm transfer to obviate the possibility of luteinized unruptured follicle syndrome, assist oocyte release, and ensure gamete intermixing. It also can be used to reduce the number of ovulating oocytes and thus to reduce the risk of multiple gestations. Follicle aspiration, sperm injection, and assisted rupture is a new, simple, office-based procedure that does not require embryologic expertise beyond sperm preparation as for IUI, yet promises to be more successful than IUI.