BIRTH OF HEALTHY NEONATE FOLLOWING PREIMPLANTATION GENETIC DIAGNOSIS IN A MOTHER WITH MOSAIC TURNER SYNDROME. CASE REPORT AND REVIEW OF THE LITERATURE.

OBJECTIVE: To report the case of a patient with mosaic Turner syndrome who underwent assisted reproduction treatment with preimplantation genetic testing for aneuploidy and gave birth to a healthy baby girl with normal karyotype; and to conduct a review of the literature on the usefulness of preimplantation genetic diagnosis in women with Turner syndrome. METHODS: A case of a 27 year-old woman diagnosed with mosaic Turner syndrome and secondary altered ovarian reserve, seen in a referral center for infertility management in Medellín, Colombia. The patient underwent in vitro fertilization followed by pre-implantation genetic testing to prevent transmission of Turner syndrome to her progeny. A literature search was conducted in the Medline via PubMed, Clinical Key, OVID, Embase, Lilacs, SciELO and Oxford Journals databases using the following terms: "Turner Syndrome," "Mosaic Turner," "Preimplantation Genetic Screening," "Preimplantation Genetic Testing," "Preimplantation Genetic Diagnosis," "Pregnancy," "Successful pregnancy." Inclusion criteria were case series and case reports, cohort studies and review articles published between January 1980 and June 2017 that included women with Turner syndrome achieving pregnancy by means of in vitro fertilization techniques with their own oocytes and who had undergone embryo biopsy for preimplantation genetic diagnosis. The search was limited to articles in Spanish and English. RESULTS: one study met the inclusion criteria. Both in this report and in our case, patients with mosaic Turner syndrome underwent several cycles of intracytoplasmic sperm injection (ICSI) with their own eggs, then performed embryonic biopsy for preimplantation genetic analysis using different techniques. In both cases, euploid embryos were transferred to the uterus with the subsequent birth of healthy girls with normal karyotype. CONCLUSIONS: Patients with mosaic Turner syndrome could benefit from preimplantation biopsy and genetic analysis to prevent transmission of the genetic defect to their progeny.

TITULO: RECIÉN NACIDO SANO DESPUÉS DE DIAGNÓSTICO GENÉTICO PREIMPLANTATORIO EN UNA MADRE CON SÍNDROME DE TURNER MOSAICO. REPORTE DE CASO Y REVISIÓN DE LA LITERATURA. OBJETIVO: reportar el caso de una paciente con síndrome de Turner en mosaico, a quien se le realizó un tratamiento de reproducción asistida con análisis genético preimplantatorio para aneuploidias, logrando el nacimiento de una niña sana con cariotipo normal, y realizar una revisión de la literatura sobre la utilidad del diagnóstico genético preimplantatorio en las mujeres con síndrome de Turner. METODOS: se presenta el caso de una mujer de 27 años, con diagnóstico de síndrome de Turner en mosaico y con alteración secundaria en la reserva ovárica, atendida en centro de referencia para el manejo de infertilidad en Medellín, Colombia, a quien se le realizó un tratamiento de fertilización in vitro con análisis genético preimplantatorio para prevenir la transmisión del síndrome de Turner a su descendencia. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed, Clinical Key, OVID, Embase, Lilacs, SciELO y Oxford Journals, con los siguientes términos: "Turner Syndrome", "Mosaic Turner", "Preimplantation Genetic Screening", "Preimplantation Genetic Testing", "Preimplantation Genetic Diagnosis", "Pregnancy", "Successful pregnancy". Como criterios de inclusión se consideraron artículos tipo series y reportes de casos, cohortes y artículos de revisión desde enero de 1980 hasta junio de 2017, que incluyeran mujeres con síndrome de Turner embarazadas por medio de técnicas de fertilización in vitro, con sus propios óvulos, y que hubiesen sido sometidas a biopsia embrionaria para diagnóstico genético preimplantatorio. La búsqueda se limitó a los idiomas español e inglés. RESULTADOS: un estudio cumplió con los criterios de inclusión. Tanto en este reporte como en nuestro caso, las pacientes con síndrome de Turner en mosaico se sometieron a varios ciclos de inyección intracitoplasmática de espermatozoides (ICSI) con sus propios óvulos, luego se realizó biopsia embrionaria para análisis genético preimplantatorio utilizando diferentes técnicas. En ambos casos se logró la transferencia al útero de embriones euploides con el posterior nacimiento de niñas sanas con cariotipo normal. CONCLUSIONES: Las pacientes con ST mosaico podrían beneficiarse de la biopsia embrionaria y análisis genético preimplantatorio para prevenir la transmisión del defecto genético a su descendencia. Palabras clave: síndrome de Turner; aneuploidía; diagnóstico preimplantación; análisis genético preimplantatorio; reserva ovárica.

Birth of healthy neonate following preimplantation genetic diagnosis in a mother with mosaic Turner syndrome. Case report and review of the literature / Recién nacido sano después de diagnóstico genético preimplantatorio en una madre con síndrome de turner mosaico. reporte de caso y revisión de la literatura

RESUMEN Objetivos: reportar el caso de una paciente con síndrome de Turner en mosaico, a quien se le realizó un tratamiento de reproducción asistida con análisis genético preimplantatorio para aneuploidias, logrando el nacimiento de una niña sana con cariotipo normal, y realizar una revisión de la literatura sobre la utilidad del diagnóstico genético preimplantatorio en las mujeres con síndrome de Turner. Materiales y métodos: se presenta el caso de una mujer de 27 años, con diagnóstico de síndrome de Turner en mosaico y con alteración secundaria en la reserva ovárica, atendida en centro de referencia para el manejo de infertilidad en Medellín, Colombia, a quien se le realizó un tratamiento de fertilización in vitro con análisis genético preimplan-tatorio para prevenir la transmisión del síndrome de Turner a su descendencia. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed, Clinical Key, OVID, Embase, Lilacs, SciE- LO y Oxford Journals, con los siguientes términos: "Turner Syndrome", "Mosaic Turner", "Preim- plantation Genetic Screening", "Preimplantation Genetic Testing", "Preimplantation Genetic Diagnosis", "Pregnancy", "Successful pregnancy". Como criterios de inclusión se consideraron artículos tipo series y reportes de casos, cohortes y artículos de revisión desde enero de 1980 hasta junio de 2017, que incluyeran mujeres con síndrome de Turner embarazadas por medio de técnicas de fertilización in vitro, con sus propios óvulos, y que hubiesen sido sometidas a biopsia embrionaria para diagnóstico genético preimplantatorio. La búsqueda se limitó a los idiomas español e inglés. Resultados: un estudio cumplió con los criterios de inclusión. Tanto en este reporte como en nuestro caso, las pacientes con síndrome de Turner en mosaico se sometieron a varios ciclos de inyección intracitoplasmática de espermatozoides (ICSI) con sus propios óvulos, luego se realizó biopsia em- brionaria para análisis genético preimplantatorio utilizando diferentes técnicas. En ambos casos se logró la transferencia al útero de embriones euploides con el posterior nacimiento de niñas sanas con cariotipo normal. Conclusión: Las pacientes con ST mosaico podrían beneficiarse de la biopsia embrionaria y análisis genético preimplantatorio para prevenir la transmisión del defecto genético a su descendencia.

ABSTRACT Objectives: To report the case of a patient with mosaic Turner syndrome who underwent assisted reproduction treatment with preimplantation genetic testing for aneuploidy and gave birth to a healthy baby girl with normal karyotype; and to conduct a review of the literature on the usefulness of preimplantation genetic diagnosis in women with Turner syndrome. Materials and methods: A case of a 27 year-old woman diagnosed with mosaic Turner syndrome and secondary altered ovarian reserve, seen in a referral center for infertility management in Medellín, Colombia. The patient underwent in vitro fertilization followed by pre-implantation genetic testing to prevent transmission of Turner syndrome to her progeny. A literature search was conducted in the Medline via PubMed, Clinical Key, OVID, Embase, Lilacs, SciELO and Oxford Journals data- bases using the following terms: "Turner Syndrome," "Mosaic Turner," "Preimplantation Genetic Screening," "Preimplantation Genetic Testing," "Preimplantation Genetic Diagnosis," "Pregnancy," "Successful pregnancy." Inclusion criteria were case series and case reports, cohort studies and review articles published between January 1980 and June 2017 that included women with Turner syndrome achieving pregnancy by means of in vitro fertilization techniques with their own oocytes and who had undergone embryo biopsy for preimplantation genetic diagnosis. The search was limited to articles in Spanish and English. Results: one study met the inclusion criteria. Both in this report and in our case, patients with mosaic Turner syndrome underwent several cycles of intracytoplasmic sperm injection (ICSI) with their own eggs, then performed embryonic biopsy for preimplantation genetic analysis using different techniques. In both cases, euploid embryos were transferred to the uterus with the subsequent birth of healthy girls with normal karyotype. Conclusion: Patients with mosaic Turner syndrome could benefit from preimplantation biopsy and genetic analysis to prevent transmission of the genetic defect to their progeny.

Morcellation for Gynecologic Surgery.

Morcellation is necessary for many women with fibroids who choose to undergo laparoscopic myomectomy or hysterectomy. After open and laparoscopic myomectomy, myometrial cells can be detected in the abdomen and pelvis. After morcellation, careful inspection for and removal of tissue fragments and copious irrigation and suctioning of fluid can remove residual tissue with or without the use of containment bags. Leiomyosarcoma has a poor prognosis because of early hematogenous metastasis and has a high propensity for recurrence despite the performance of total abdominal hysterectomy. Eliminating residual tissue in the pelvis and abdomen should be the goal after morcellation.

Alternative facts and morcellation.

PURPOSE OF REVIEW: Since the recent black-box warning regarding the use of electromechanical morcellation, there has been a hesitancy to utilize the product and even to perform other types of morcellation by gynecologists. Unfortunately, this Food and Drug Administration action and the continued public criticisms of this procedure are grounded in poor data and faulty reasoning. To truly perform informed consent to patients considering procedures involving morcellation, a thorough review of the facts, not alternative facts, must be communicated. RECENT FINDINGS: Misrepresentation of the ethics surrounding this procedure, the role of informed consent and the risks and benefits as determined by evidence-based medicine have led to confusion and poor public policy. Today's evidence suggests that the procedure is indeed ethical when full disclosure of the risks and benefits is presented via informed consent. Risks of the procedure have been exaggerated significantly, and little attention has been paid to the risks of denying morcellation procedures to patients. Attempts to condemn gynecologists as acting contrary to established surgical principles do not coincide with facts. SUMMARY: Morcellation is a controversial technique which undoubtedly has a role as well as limitations. To appropriately determine if the procedure is indicated and acceptable to the patient, full disclosure of the best available evidence is necessary.

Agility in adversity: Vaccines on Demand.

Is the US ready for a biological attack using Ebola virus or Anthrax? Will vaccine developers be able to produce a Zika virus vaccine, before the epidemic spreads around the world? A recent report by The Blue Ribbon Study Panel on Biodefense argues that the US is not ready for these challenges, however, technologies and capabilities that could address these deficiencies are within reach. Vaccine technologies have advanced and readiness has improved in recent years, due to advances in sequencing technology and computational power making the 'vaccines on demand' concept a reality. Building a robust strategy to design effective biodefense vaccines from genome sequences harvested by real-time biosurveillance will benefit from technologies that are being brought to bear on the cancer cure 'moonshot'. When combined with flexible vaccine production platforms, vaccines on demand will relegate expensive and, in some cases, insufficiently effective vaccine stockpiles to the dust heap of history.

What is the Future of Open Intraperitoneal Power-Morcellation of Fibroids?

In November 2014, the Food and Drug Administration (FDA) calculated that for every 498 women having surgery for presumed fibroids, one woman would be found to have an occult leiomyosarcoma (LMS). The FDA issued a safety communication warning against the use of laparoscopic morcellators in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids. This communication was prompted by concern that if a patient had an occult LMS, the morcellator might spread tumor cells within the peritoneal cavity. We submit that the FDA directive was based on a flawed and misleading analysis. More rigorous evidence estimates the prevalence of LMS among women operated upon for presumed uterine fibroids at approximately one in 2000 women, significantly lower than the FDA's estimate. In addition, there is no reliable evidence that morcellation influences survival or that power-morcellation is inferior to vaginal or mini-lap morcellation with a scalpel. Recent publication shows that open surgery carries more risk for women when compared with minimally invasive surgery. Although the possibility of occult LMS should be considered by women and their gynecologists, we suggest that current morcellation techniques be continued for women who wish to benefit from minimally invasive surgery. Investigation into new and, hopefully, better morcellating devices may make the procedure safer for women.

U.S. Food and Drug Administration's Guidance Regarding Morcellation of Leiomyomas: Well-Intentioned, But Is It Harmful for Women?

The U.S. Food and Drug Administration (FDA) is warning against the use of laparoscopic power morcellators in the majority of women undergoing myomectomy or hysterectomy for the treatment of leiomyomas because of the concern for inadvertent spread of tumor cells if an undiagnosed cancer were present. The authors, representing a 45-member review group, reviewed the current literature to formulate prevalence rates of leiomyosarcoma in women with presumed leiomyomas and to asses reliable data regarding patient survival after morcellation. The authors disagree with the FDA's methodology in reaching their conclusion and provide clinical recommendations for care of women with leiomyomas who are planning surgery.

The prevalence of occult leiomyosarcoma at surgery for presumed uterine fibroids: a meta-analysis.

There is a concern regarding the risk of occult leiomyosarcomas found at surgery for presumed benign fibroids. We sought to produce a comprehensive review of published data addressing this issue and provide high-quality prevalence estimates for clinical practice and future research. A comprehensive literature search using the PubMed/MEDLINE database and the Cochrane Library was performed. Inclusion criteria were human studies, peer-reviewed, with original data, involving cases for surgery in which fibroid-related indications were the primary reason for surgery, and histopathology was provided. Candidate studies (4864) were found; 3844 were excluded after review of the abstract. The remaining 1020 manuscripts were reviewed in their entirety, and 133 were included in the Bayesian binomial random effect meta-analysis. The estimated rate of leiomyosarcoma was 0.51 per 1000 procedures (95 % credible interval (CrI) 0.16-0.98) or approximately 1 in 2000. Restricting the meta-analysis to the 64 prospective studies resulted in a substantially lower estimate of 0.12 leiomyosarcomas per 1000 procedures (95 % CrI <0.01-0.75) or approximately 1 leiomyosarcoma per 8300 surgeries. Results suggest that the prevalence of occult leiomyosarcomas at surgery for presumed uterine fibroids is much less frequent than previously estimated. This rate should be incorporated into both clinical practice and future research.

Outcome of occult uterine leiomyosarcoma after surgery for presumed uterine fibroids: a systematic review.

There is concern that morcellation of occult leiomyosarcomas during surgery to treat presumed myomas may substantially worsen patient outcome. We reviewed the existing medical literature to better understand whether such a risk was demonstrable and, if so, what the magnitude of that risk might be. We identified 4864 articles initially, of which 60 were evaluated in full. Seventeen were found to have outcomes information and are included in this review. Six studies addressed the question of whether morcellation of occult leiomyosarcomas resulted in inferior outcomes as compared with en bloc uterine and tumor removal. In these 6 studies, results suggested that en bloc removal may result in improved survival and less recurrence; however, the data are highly biased and of poor quality. There is no reliable evidence that morcellation, power or otherwise, substantially results in tumor upstaging. There is no evidence from these 17 studies that power morcellation differs in any way from other types of morcellation or even simple myomectomy insofar as patient outcome. Whether electromechanical morcellation poses a unique danger to the patient with occult leiomyosarcoma is an unanswered question and one clearly in need of more extensive investigation before conclusions are drawn and policies created.

Laparoscopic surgery for endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity and is associated with pain and subfertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy. OBJECTIVES: To assess the effectiveness and safety of laparoscopic surgery in the treatment of painful symptoms and subfertility associated with endometriosis. SEARCH METHODS: This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group including searching CENTRAL, MEDLINE, EMBASE, PsycINFO, and trial registries from inception to July 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) were selected in which the effectiveness and safety of laparoscopic surgery used to treat pain or subfertility associated with endometriosis was compared with any other laparoscopic or robotic intervention, holistic or medical treatment or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Selection of studies, assessment of trial quality and extraction of relevant data were performed independently by two review authors with disagreements resolved by a third review author. The quality of evidence was evaluated using GRADE methods. MAIN RESULTS: Ten RCTs were included in the review. The studies randomised 973 participants experiencing pain or subfertility associated with endometriosis. Five RCTs compared laparoscopic ablation or excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus ablation. One RCT compared laparoscopic ablation versus diagnostic laparoscopy and injectable gonadotropin-releasing hormone analogue (GnRHa) (goserelin) with add-back therapy. Common limitations in the primary studies included lack of clearly-described blinding, failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias.Laparoscopic surgery was associated with decreased overall pain (measured as 'pain better or improved') compared with diagnostic laparoscopy, both at six months (odds ratio (OR) 6.58, 95% CI 3.31 to 13.10, 3 RCTs, 171 participants, I(2) = 0%, moderate quality evidence) and at 12 months (OR 10.00, 95% CI 3.21 to 31.17, 1 RCT, 69 participants, low quality evidence). Compared with diagnostic laparoscopy, laparoscopic surgery was also associated with an increased live birth or ongoing pregnancy rate (OR 1.94, 95% CI 1.20 to 3.16, P = 0.007, 2 RCTs, 382 participants, I(2) = 0%, moderate quality evidence) and increased clinical pregnancy rate (OR 1.89, 95% CI 1.25 to 2.86, P = 0.003, 3 RCTs, 528 participants, I(2) = 0%, moderate quality evidence). Two studies collected data on adverse events (including infection, vascular and visceral injury and conversion to laparotomy) and reported no events in either arm. Other studies did not report this outcome. The similar effect of laparoscopic surgery and diagnostic laparotomy on the rate of miscarriage per pregnancy was imprecise (OR 0.94, 95% CI 0.35 to 2.54, 2 studies, 112 women, moderate quality evidence).When laparoscopic ablation was compared with diagnostic laparoscopy plus medical therapy (GnRHa plus add-back therapy), more women in the ablation group reported that they were pain free at 12 months (OR 5.63, 95% CI 1.18 to 26.85, 1 RCT, 35 participants, low quality evidence).The difference between laparoscopic ablation and laparoscopic excision in the proportion of women reporting overall pain relief at 12 months on a VAS 0 to 10 pain scale was 0 (95% CI -1.22 to 1.22, P = 1.00, 1 RCT, 103 participants, low quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis reduces overall pain and increases live birth or ongoing pregnancy rates. There is low quality evidence that laparoscopic excision and ablation were similarly effective in relieving pain, although there was only one relevant study. More research is needed considering severe endometriosis, different types of pain associated with endometriosis (for example dysmenorrhoea (pain with menstruation)) and comparing laparoscopic interventions with holistic and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

The surgical treatment of fibroids for infertility.

Uterine fibroids are a major gynecologic disorder among women and commonly found in the infertile couple. Although numerous surgical techniques exist to destroy or remove these tumors, the role of such surgical procedures in the infertile woman has been heavily debated. The primary reason for this is a lack of evidence of a cause-and-effect relationship between fibroids and subfertility. However, review of the evidence suggests that submucous myomas and possibly intramural myomas both serve to decrease female fertility. A second reason for caution is concern over the impact of surgical treatment on fertility enhancement. For submucous myomas, hysteroscopic myomectomy has proven capable of increasing fertility rates, although this statement may not apply to type 2 submucous myomas. No evidence currently exists for a beneficial effect on fertility of surgical intervention for intramural or subserous fibroids. More randomized treatment trials are clearly needed to clarify the role of myomectomy and other procedures in the infertile woman with type 2 submucous and intramural myomas.

Fibroids and reproduction.

Uterine fibroids are commonly seen in women with reproductive disorders such as infertility, spontaneous abortion (SAB), and obstetric complications. Although it is certain that these tumors can occasionally cause such pathophysiology, it is critical to understand the rate of such occurrences, the degree of causality of the fibroids, and our ability to ameliorate the problems via surgical treatment. Evaluation of the available data is hampered by poor quality studies, heterogeneity of the disease, and confounding factors affecting outcomes. Nevertheless, the best available evidence suggests the following: (1) Submucous myomas decrease fertility and increase SAB rates; myomectomy is likely to be of value; (2) intramural myomas may decrease fertility, but the issue is less clear; they do seem to increase rates of miscarriage; there is no solid evidence that myomectomy restores the patient to normal; (3) subserosal myomas do not impair fertility but may enhance the rate of SAB; and (4) fibroids increase the risk of several obstetric complications, including cesarean delivery, malpresentation, postpartum hemorrhage, retained placenta, intrauterine growth retardation, preterm labor, placenta previa, and abruption. Higher quality studies are desperately needed to add confidence to these tenuous conclusions.