Elevated Anti-Müllerian Hormone as a Prognostic Factor for Poor Outcomes of In Vitro Fertilization in Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) tend to have elevated anti-Müllerian hormone (AMH) levels, which appear to correlate with disease severity and pregnancy outcomes. This was a retrospective observational study designed to assess the relationship between circulating AMH levels and in vitro fertilization (IVF) outcomes. The study involved 150 women with PCOS who underwent IVF treatments. The women's IVF cycles were allocated into three subgroups according to AMH levels: 'low' (AMH < 3.7 ng/mL; n = 49), 'middle' (AMH 3.7-7.4 ng/mL; n = 94), and 'high' (AMH > 7.4 ng/mL; n = 56). All pregnancy-related outcomes (positive beta human chorionic gonadotropin (ßHCG), clinical pregnancy rate, live birth rate, and cumulative live birth rate) were greater in women's IVF cycles with 'low' AMH when compared to those with 'middle' or 'high' AMH (p < 0.05). AMH levels below 3.7 ng/mL were found to be associated with lower oocyte immaturity rate and better pregnancy outcomes, although baseline AMH was not shown to have any significant predictive power for live birth and cumulative live birth in the multivariable logistic regression analysis after adjusting for possible confounders nor in the ROC analyses. In summary, the current study lays the groundwork to validate high AMH levels as a poor prognostic factor for pregnancy outcomes after IVF in women with PCOS.

Female Reproductive Health - study of an egg donor population.

OBJECTIVE: Infertility is one of the most significant reproductive health issues addressed with medically assisted procreation. This study looked into a potential correlation between the number of mature oocytes harvested and donor biological characteristics in order to propose an anti-Müllerian hormone (AMH) cutoff level to optimize the selection of candidates for gamete donation. METHODS: The donors were healthy women included in the Public Gamete Bank between 2011 and 2021. Their results can be used as a national indicator of fertility. RESULTS: We found that women with higher AMH levels had more antral follicles and oocytes harvested. As age increased, the number of oocytes harvested decreased. The suggested AMH cutoff level for successful donation was 1.12 ng/mL. CONCLUSIONS: The analysis of the reproductive health of Public Gamete Bank donors allows the standardization of AMH cutoff values at a national level, since the same laboratory techniques were employed consistently across medical centers. The study also allowed insight into the factors that compromise donation success. If adopted, a more rigorous selection of donor candidates would increase the success rate of egg donations.

Preservation of fertility in female patients with hematologic diseases.

Recent developments of assisted reproduction techniques turned possible to avoid the infertility consequences of oncologic treatments, but fertility preservation (FP) has been somewhat neglected in women with hematologic diseases undergoing gonadotoxic treatments. For these specific cases, the current options for FP include the cryopreservation of embryos, mature oocytes and ovarian tissue, and oocyte in-vitro maturation. We intend to make patients and clinicians aware of this important and relevant issue, and provide hematologists, assisted reproduction physicians and patients, with updated tools to guide decisions for FP. The physicians of the units responsible for female FP should always be available to decide on the best-individualized FP option in strict collaboration with hematologists. With a wide range of options for FP tailored to each case, a greater level of training and information is needed among clinicians, so that patients proposed to gonadotoxic treatments can be previously advised for FP techniques in hematological conditions. ABBREVIATED ABSTRACT: Recent developments of assisted reproduction techniques turned possible to preserve the fertility of women with hematologic diseases undergoing gonadotoxic treatments. Current options for fertility preservation in women with hematologic diseases are presented. It is imperative to offer fertility preservation to all women before starting any gonadotoxic treatment and in some cases after treatment. Fertility preservation methods enable to later achieve the desired pregnancy.

Follicular fluid composition and reproductive outcomes of women with polycystic ovary syndrome undergoing in vitro fertilization: A systematic review.

Polycystic ovary syndrome (PCOS) is recognized as one of the most prevalent endocrinopathy in women at reproductive age. As affected women tend to have poorer assisted reproductive technology (ART) outcomes, PCOS has been suggested to endanger oocyte quality and competence development. The aim of this systematic review was to summarize the available evidence on how the follicular fluid (FF) profile of women with PCOS undergoing in vitro fertilization (IVF) treatment differs from the FF of normo-ovulatory women. For that, an electronic search in PubMed and Web of Science databases was conducted (up to December 2021). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA guidelines were followed, and the Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies. Data retrieved from papers included (n=42), revealed that the FF composition of women with PCOS compared to those without PCOS predominantly diverged at the following molecular classes: oxidative stress, inflammatory biomarkers, growth factors and hormones. Among those biomarkers, some were proposed as being closely related to pathophysiological processes, strengthening the hypothesis that low-grade inflammation and oxidative stress play a critical role in the pathogenesis of PCOS. Notwithstanding, it should be noticed that the available data on PCOS FF fingerprints derives from a limited number of studies conducted in a relatively small number of subjects. Furthermore, phenotypic heterogeneity of PCOS hampers wider comparisons and weakens putative conclusions. Therefore, future studies should be focused at comparing well characterized patient subgroups according to phenotypes.

Candidates selection for oocyte donation in a public gamete bank-Predictive value of the anti-Müllerian hormone.

Background: Infertility treatments with oocyte donation are becoming frequent. Recruitment of oocyte donors is a demanding and costly process and therefore of crucial importance. The selection of the oocyte donors undergoes a rigorous evaluation process of the candidates with routine measurement of the anti-Müllerian hormone (AMH) levels (ovarian reserve test). Our aim was to assess whether AMH levels could act as a good marker as tool to select the donor candidates and correlate them with the ovarian response to stimulation with a gonadotropin-releasing hormone antagonist protocol as well as to identify and validate the appropriate AMH level threshold by correlating it with the number of oocytes retrieved. Methods: A retrospective analysis of the oocyte donors' clinical records was performed. Results: The mean age of the participants was 27 years. The ovarian reserve evaluation showed a mean AMH of 5.20 ng/mL. An average number of 16 oocytes was retrieved (12 mature oocytes MII). AMH levels showed a statistically significant positive correlation with the number of total oocytes retrieved. A threshold value of AMH = 3.2 ng/mL predictive of the retrieval <12 oocytes (areas under the curve, 0.7364; 95% confidence interval: 0.529-0.944) was identified by receiver operating characteristic curve. Using this cutoff, the normal response (12 oocytes) was predicted with a sensitivity of 77% and a specificity of 60%. Conclusions: The measurement of AMH may be a determining factor in the choice of the oocyte donor candidates to maximize the response to requests from beneficiaries who require donor oocytes to perform assisted reproductive technique cycles.

All that glitters is not gold: a stereological study of human donor oocytes.

Here we report a quantitative analysis of human metaphase II (MII) oocytes from a 22-year-old oocyte donor, retrieved after ovarian-controlled hyperstimulation. Five surplus donor oocytes were processed for transmission electron microscopy (TEM), and a stereological analysis was used to quantify the distribution of organelles, using the point-counting technique with an adequate stereological grid. Comparisons between means of the relative volumes (Vv) occupied by organelles in the three oocyte regions, cortex (C), subcortex (SC) and inner cytoplasm (IC), followed the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction. Life cell imaging and TEM analysis confirmed donor oocyte nuclear maturity. Results showed that the most abundant organelles were smooth endoplasmic reticulum (SER) elements (26.8%) and mitochondria (5.49%). Significant differences between oocyte regions were found for lysosomes (P = 0.003), cortical vesicles (P = 0.002) and large SER vesicles (P = 0.009). These results were quantitatively compared with previous results using prophase I (GV) and metaphase I (MI) immature oocytes. In donor MII oocytes there was a normal presence of cortical vesicles, SER tubules, SER small, medium and large vesicles, lysosomes and mitochondria. However, donor MII oocytes displayed signs of cytoplasmic immaturity, namely the presence of dictyosomes, present in GV oocytes and rare in MI oocytes, of SER very large vesicles, characteristic of GV oocytes, and the rarity of SER tubular aggregates. Results therefore indicate that the criterion of nuclear maturity used for donor oocyte selection does not always correspond to cytoplasmic maturity, which can partially explain implantation failures with the use of donor oocytes.

Genetic counseling and carrier screening in candidates for gamete donation at a Portuguese center.

OBJECTIVE: Genetic counseling and carrier screening are part of the gamete donation process by healthy individuals. We aim to review the findings of genetic counseling and carrier screening of a cohort of candidates at our public gametes bank. METHODS: Thirty-four male and 64 female candidates had genetic counseling with a medical geneticist before donation. Of these, one female candidate voluntarily dropped-out. Thirty-four males and 63 females performed karyotype and screening for the more common pathogenic variants for CFTR-related cystic fibrosis and spinal muscular atrophy (SMN1) in the Portuguese population. In addition, all females also performed Fragile X expansion screening (FMR1). Thirty candidates with known or assumed African ancestry performed hemoglobinopathies screening. RESULTS: Six candidates were definitely or temporarily withheld from the donation process given their family or personal history that required further investigation. Of 97 candidates tested, 16.5% presented anomalous laboratory results (16/97): ten candidates were carriers for an autosomal recessive disorder - cystic fibrosis (5/97), sickle cell anemia (3/30), and spinal muscular atrophy (2/97). One female was an FMR1 pre-mutation carrier (1/63). One female candidate presented with triple X mosaicism: 47,XXX[2]/46,XX[50]. Two candidates presented with chromosomal instability of unknown origin. In one candidate, a mosaic for the Philadelphia chromosome was detected, revealing the diagnosis of chronic myeloid leukemia. CONCLUSIONS: From a cohort of 97 candidates, 21.7% had a family/personal history or an anomalous laboratory result that required additional genetic counseling, stressing the importance of performing pre-donation genetic counseling in this population.

Male Reproductive Health - study of a sperm donor population.

OBJECTIVE: Every individual has the right to a safe and satisfactory sex and reproductive life. Therefore, several countries have made efforts to make Reproductive Health resources available to their populations. However, few results have been published regarding the policies implemented in Portugal. This study looked into the reproductive health status of the Portuguese male population. METHODS: Sperm donor candidates from the Portuguese Public Gamete Bank registered between 2011 and 2018 were included in the study. Spermogram findings were evaluated with respect to sociodemographic and risk factors. RESULTS: This is the first study performed in this population. We found that sperm quality has decreased throughout the last nine years, and that spermatozoa progressive motility is inversely correlated with the body mass index. An association between drug use and decreased sperm pH was also found. CONCLUSIONS: Changes in sperm quality have important consequences in male fertility. Most of the identified causes of decreased sperm quality are modifiable factors and should therefore be addressed since an early age.

Use of the FMR1 Gene Methylation Status to Assess the X-Chromosome Inactivation Pattern: A Stepwise Analysis.

X-chromosome inactivation (XCI) is a developmental process to compensate the imbalance in the dosage of X-chromosomal genes in females. A skewing of the XCI pattern may suggest a carrier status for an X-linked disease or explain the presence of a severe phenotype. In these cases, it is important to determine the XCI pattern, conventionally using the gold standard Human Androgen-Receptor Assay (HUMARA), based on the analysis of the methylation status at a polymorphic CAG region in the first exon of the human androgen receptor gene (AR). The aim of this study was to evaluate whether the methylation status of the fragile mental retardation protein translational regulator gene (FMR1) can provide an XCI pattern similar to that obtained by HUMARA. A set of 48 female carriers of FMR1 gene normal-sized alleles was examined using two assays: HUMARA and a FMR1 methylation PCR (mPCR). Ranges were defined to establish the XCI pattern using the methylation pattern of the FMR1 gene by mPCR. Overall, a 77% concordance of the XCI patterns was obtained between the two assays, which led us to propose a set of key points and a stepwise analysis towards obtaining an accurate result for the XCI pattern and to minimize the underlying pitfalls.

Influence of Women´s Residence Region on Assisted Reproduction Treatments - Experience of a Tertiary Center in Northern Portugal.

OBJECTIVE: Data on the possible influence of women´s region of residence, within the same country, on the outcomes of medically assisted reproduction cycles are scarce. This study aims to assess the impact of the women's region of residence on the results of in-vitro fertilization cycles. METHODS: We evaluated in-vitro fertilization cycles between 2010 and 2017, performed in a northern Portugal assisted reproduction center. We defined two groups: Douro Litoral (group 1; n=783), and Trás-os-Montes and Alto Douro (group 2; n=178). We analyzed demographics and cycle-related variables, and we calculated the rates for embryo transfer cycles. We used the Mann-Whitney and Chi-square tests and p<0.05 was considered statistically significant. RESULTS: We included 961 cycles. The region of residence had no effect on the following variables: women´s age; body mass index; or duration of infertility (p>0.05). Group 2 had a statistical significant lower number of previous cycles than group 1 (1.3±0.5 and 1.5±0.7; p=0.005). In the sub-analysis of cycles with embryo transfer (n=781), group 1 obtained had rates of normal fertilization (62.5% vs. 57.5%; p=0.04), miscarriage rate (30.0 vs. 10.9%; p=0.007), and lower implantation rates compared to group 2 (33.3% vs. 50.0%; p<0.001). CONCLUSIONS: Women from the region of Trás-os-Montes e Alto Douro had a lower number of previous cycles, compared to those from the Douro Litoral, despite the absence of statistical significant differences in terms of age or infertility duration. These findings reinforce the need to contemplate the sociodemographic and socioeconomic variables in this context.

Development and Validation of a Mathematical Model to Predict the Complexity of FMR1 Allele Combinations.

The polymorphic trinucleotide repetitive region in the FMR1 gene 5'UTR contains AGG interspersions, particularly in normal-sized alleles (CGG < 45). In this range repetitive stretches are typically interrupted once or twice, although alleles without or with three or more AGG interspersions can also be observed. AGG interspersions together with the total length of the repetitive region confer stability and hinder expansion to pathogenic ranges: either premutation (55 < CGG < 200) or full mutation (CGG > 200). The AGG interspersions have long been identified as one of the most important features of FMR1 repeat stability, being particularly important to determine expansion risk estimates in female premutation carriers. We sought to compute the combined AGG interspersion numbers and patterns, aiming to define FMR1 repetitive tract complexity combinations. A mathematical model, the first to compute this cumulative effect, was developed and validated using data from 131 young and healthy females. Plotting of their allelic complexity enabled the identification of two statistically distinct groups - equivalent and dissimilar allelic combinations. The outcome, a numerical parameter designated allelic score, depicts the repeat substructure of each allele, measuring the allelic complexity of the FMR1 gene including the AGGs burden, thus allowing new behavioral scrutiny of normal-sized alleles in females.

Single Fetal Death in Monochorionic Twin Pregnancy: Co-Twin Prognosis and Neonatal Outcome.

The incidence of single fetal death in twin pregnancy varies from 0.5% - 6.8%, leaving the surviving fetus with increased morbi-mortality. The prognosis is worse in monochorionic pregnancies. In addressing these cases it should be noted referral to tertiary center with differentiated perinatal support, induction of fetal lung maturation and termination of pregnancy if there's loss of fetal well-being or possibility of maternal complications and suspected neurological sequelae in the surviving fetus. The risk of iatrogenic prematurity should always be weighed with the possible consequences arising from the fetus staying in a hostile uterine environment. The authors describe a case of a 32-year-old pregnant woman with monochorionic/diamniotic twin pregnancy diagnosed with death of one of the fetuses due to fetal growth restriction and velamentous insertion of the umbilical cord at 30 weeks of gestation. The couple opted for termination of pregnancy at 33 weeks after documentation of brain changes in the surviving fetus.

A incidência de morte fetal de um feto na gestação gemelar varia de 0,5% - 6,8%, deixando o feto sobrevivente com morbi-mortalidade aumentada. O prognóstico é pior em gestações monocoriónicas. Ao abordar estes casos importa realçar a referenciação a centro terciário com apoio perinatal diferenciado, a indução da maturação pulmonar fetal e a interrupção da gravidez se houver perda de bem-estar fetal ou possibilidade de complicações maternas ou suspeita de sequelas neurológicas no feto sobrevivente, devendo os riscos da prematuridade iatrogénica serem sempre pesados com as possíveis sequelas decorrentes da permanência do feto num ambiente uterino hostil. Os autores descrevem o caso de uma mulher de 32 anos com gravidez monocoriónica/diamniótica com morte de um dos fetos, com restrição de crescimento grave e inserção velamentosa do cordão umbilical, pelas 30 semanas de gestação. O casal optou pela terminação da gravidez às 33 semanas, após documentação de alterações cerebrais no feto sobrevivente.

Infectious Postpartum Sacroiliitis: The Importance and Difficulty of Early Diagnosis.

The sacroiliitis accounts for about 1.5% - 10% of all cases of septic arthritis and it is strongly associated with gynaecological infections, pelvic trauma or drug abuse (3.4% - 12.8% of cases occur during the postpartum period). Early diagnosis is difficult because the symptoms are nonspecific in pregnancy and in the postpartum period, making the delay of treatment a serious risk of irreversible damage to the joint and development of post-infectious complications. The authors describe the case of a 37-year-old puerperal woman presented to hospital, weeks after urgent caesarean section, with endometritis, post-anesthetic epidural hematoma and secondary infectious postpartum sacroiliitis. The diagnosis of sacroiliac joints pathology during pregnancy and puerperium is challenging. The pathogenesis of infectious sacroiliitis results from local contamination by contiguous infection or hematogenous spread of bacterial infections. The prognosis is usually favorable and depends on early diagnosis and treatment.

A sacroileíte representa 1,5% - 10% de todos os casos de artrite séptica e está fortemente associada a infecções ginecológicas, trauma pélvico e a abuso de drogas (3,4% - 12,8% dos casos ocorrem durante o puerpério). O diagnóstico precoce é difícil, pois os sintomas são inespecíficos na gravidez e no puerpério, retardando o tratamento, podendo assim causar danos irreversíveis à articulação e desenvolvimento de complicações pós-infecciosas. Os autores descrevem o caso de uma puérpera de 37 anos que duas semanas após realização de cesariana urgente iniciou quadro de endometrite, hematoma epidural secundário a complicação anestésica e sacroileíte infecciosa secundária. O diagnóstico de patologia da articulação sacroilíaca durante a gravidez e puerpério constitui um desafio. A patogénese da artrite séptica resulta da contaminação local por infecção contígua ou da disseminação hematogénea. O prognóstico da sacroileíte infecciosa do pós-parto é geralmente favorável e depende do diagnóstico e tratamento precoces.

[Assisted Reproductive Technology in Female Transplant Recipients: Experience of a Reproductive Medicine Unit and Literature Review]. / Procriação Assistida em Mulheres Transplantadas: Experiência de uma Unidade de Medicina da Reprodução e Revisão da Literatura.

Diseases in end stage typically occur with hypothalamic-pituitary-ovarian axis disorders, with consequent anovulation and infertility. The solid organ transplantation increased survival of patients with end-stage organs disease and the vast majority of women improve their reproductive capacity after transplantation. Although adoption can always be a possibility, the transplanted infertile woman has the right to self-reproductive determination using assisted reproductive techniques. While it is known that pregnancies in transplantedwomen are at high risk, there is no evidence of differences in pregnancy outcome in pregnant transplanted subject to technical, compared with spontaneous pregnancies. The use of assisted reproductive techniques in transplanted women is a medical, ethical and psychosocial challenge, whose approach must be multidisciplinary, to ensure reproductive success without compromising the function of the transplanted organ or maternal health, allowing the birth of a healthy child. The literature remains scarce. Three clinical cases are presented.

Doenças em estádio terminal cursam tipicamente com distúrbios do eixo hipotálamo-hipófise-ovário, com consequente anovulação e infertilidade. A transplantação de órgãos sólidos aumentou a sobrevida e melhorou a capacidade reprodutiva das mulheres com este tipo de patologia. Embora a adopção seja uma possibilidade, a mulher transplantada infértil tem direito à sua autodeterminação reprodutiva com recurso a técnicas de procriação medicamente assistida. As gravidezes em mulheres transplantadas são de alto risco, mas não parece existir evidência de diferenças no desfecho obstétrico e neonatal nas grávidas transplantadas sujeitas a procriação assistida, comparativamente a gravidezes espontâneas. A utilização de técnicas de procriação assistida em mulheres transplantadas constitui um desafio médico, ético e psicossocial, cuja abordagem deve ser multidisciplinar, para assegurar o sucesso reprodutivo sem comprometer a função do órgão transplantado ou a saúde materna, permitindo o nascimento de uma criança saudável. A literatura existente mantém-se escassa. São apresentados três casos clínicos.

[Uterine Rupture at 18 Weeks of Pregnancy in the Context of Malformed Uterus]. / Rotura Uterina às 18 Semanas de Gravidez no Contexto de Útero Malformado.

Birth defects of the female genital tract are relatively common and often asymptomatic. Despite the pregnancy outcome can be favorable, adverse obstetric outcomes are described in women with uterine malformations. The authors report the case of an obstetric emergency which enhances the possibility of a very adverse and rare outcome of uterine rupture in a left hemi-cavity of a bicornuate uterus away from the term, at 18 weeks of pregnancy, in a pregnant woman with history of caesarean in the right hemi-cavity and with placenta increta. A malformed uterus with a primitive type cavity has lower distensibility of the wall with the progression of the pregnancy and facilitates the development of abnormal placentation forms, increasing the risk of uterine rupture in the first and second trimesters. The knowledge of the existence of a congenital uterine anomaly in the preconceptional period is of primary importance.

As malformações congénitas do tracto genital feminino são relativamente comuns e frequentemente assintomáticas. Apesar do resultado da gravidez poder ser favorável, estão descritos desfechos obstétricos adversos em mulheres com malformações uterinas. Os autores apresentam o caso clínico de uma emergência obstétrica, que realça a possibilidade de um desfecho muito adverso e raro, de rotura uterina da hemicavidade esquerda num útero bicórneo longe do termo, às 18 semanas de gestação, numa grávida com antecedentes de cesariana na hemicavidade direita e com placenta increta. Um útero malformado, com cavidade de tipo rudimentar, apresenta menor distensibilidade da parede com a progressão da gravidez e facilita o desenvolvimento de formas anormais de placentação, aumentando o risco de rotura uterina no primeiro e segundo trimestres. O conhecimento da existência de uma malformaçãouterina no período pré-concepcional reveste-se de importância fundamental.