The correct answer is 1. This is because hysterosalpingography determines if there is any obstruction of the tubes and, therefore, fertilization does not occur. This is not the case in our patient, where fertilization does occur and even implantation occurs. The rest of the diagnostic tests would be included.

[HIDDEN] This is because hysterosalpingography determines if there is any obstruction of the tubes and, therefore, fertilization does not occur. This is not the case in our patient, where fertilization does occur and even implantation occurs. The rest of the diagnostic tests would be included.

A 36-year-old woman comes to the clinic because she has had three miscarriages in the first trimester. She has not had any full-term pregnancies. The studies that you will request in the first term are NOT included:

Peripheral blood karyotyping of both partners.

Determination of antiphospholipid antibodies.

Future pregnancy outcome in unexplained recurrent first trimester miscarriage.

The future pregnancy outcome of 201 consecutive women, median age 34 years (range 22-43), with a history of unexplained recurrent first trimester miscarriage (median 3; range 3-13), was studied. All women and their partners had normal peripheral blood karyotypes; none had antiphospholipid antibodies and none hypersecreted luteinizing hormone (LH). No pharmacological treatment was prescribed and early pregnancy supportive care was encouraged. Women aged < or = 30 years had a subsequent miscarriage rate of 25% (14/57) which rose to 52% (13/25) in women aged > or = 40 years (P = 0.02). After three consecutive miscarriages, the risk of miscarriage of the next pregnancy was 29% (34/119) but increased to 53% (9/17) after six or more previous losses (P = 0.04). A past history of a livebirth did not influence the outcome of the next pregnancy. Supportive care in early pregnancy conferred a significant beneficial effect on pregnancy outcome. Of 160 women who attended the early pregnancy clinic, 42 (26%) miscarried in the next pregnancy compared with 21 out of 41 (51%) who did not attend the clinic (P = 0.002). After thorough investigation, women with unexplained recurrent first trimester miscarriage have an excellent pregnancy outcome without pharmacological intervention if offered supportive care alone in the setting of a dedicated miscarriage clinic.

Evaluation of basal hormone levels and androgen receptor gene mutations in individuals with recurrent abortion.

A recurrent miscarriage is at least two consecutive miscarriages in the first trimester of pregnancy. Due to the dependence of pregnancy on endocrine changes in the menstrual cycle, its disorders can also affect the outcome of pregnancy. In addition to hormonal disorders, genetic changes are essential factors in recurrent miscarriage. The development and maturation of ovulation depend on the molecular signaling pathways that respond to androgens. Hundreds of mutations leading to resistance to androgen receptor (AR) gene function have been recorded, including the 5'UTR polymorphic region. Therefore, considering the role of androgen receptors and hormonal changes in recurrent miscarriage, this study was performed to investigate the relationship between hormonal changes and AR gene mutations in patients with recurrent miscarriage. In this regard, a case-control study was performed on 150 patients with miscarriage referred to the infertility center. Hysterosalpingography, parental karyotype, vaginal ultrasound, antiphospholipid antibody measurement, anticardiolipin antibody, history and physical examination were performed to evaluate the possible causes of recurrent miscarriage. Hormone levels of LH, FSH, TSH, and Prolactin were measured and compared in two groups with known and unknown causes. Blood samples were also taken from patients, and after DNA extraction, the PCR method was used to determine AR gene mutations. The mean age was 30.2 ± 7.1 years, the mean number of abortions was 2.6 ± 1.2, and the mean duration of marriage was 6.1 ± 2.1 years. The mean of hormones in the two groups with known and unknown causes was compared, that TSH was significantly lower in the group with unknown cause (P = 0.031) and prolactin was higher in recurrent miscarriage patients with polycystic ovaries (P = 0.048). Regarding genetic evaluation, in the 5'UTR region of the androgen receptor gene, deletion of T nucleotide was observed in the +25 position, but no significant difference was found between the two groups. Generally, the findings of this study showed that thyroid dysfunction and hyperprolactinemia should be considered as an endocrine disorder in people with recurrent miscarriage, and genetic evaluation showed that the AR gene mutation was not associated with recurrent miscarriage.

Recurrent miscarriage

Immune factors A common feature of immune factors in causing recurrent pregnancy loss appears to be a decreased maternal immune tolerance towards the fetus. Antiphospholipid syndrome The antiphospholipid syndrome is an autoimmune disease that is a common cause of recurrent pregnancy loss. Around 15% of the women who have recurrent miscarriages have high levels of antiphospholipid antibodies. Women who have had more than one miscarriage in the first trimester, or a miscarriage in the second trimester, may have their blood tested for antibodies, to determine if they have antiphospholipid syndrome. Women diagnosed with antiphospholipid syndrome generally take aspirin or heparin in subsequent pregnancies, but questions remain due to the lack of high quality trials. Thyroid antibodies Anti-thyroid autoantibodies are associated with an increased risk of recurrent miscarriage with an odds ratio of 2.3 with a 95% confidence interval of 1.5–3.5. Increased uterine NK cells

The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages.

To determine the prevalence of lupus anticoagulant and raised anticardiolipin antibodies in women with a history of two or more miscarriages in the first trimester of pregnancy. A prospective study of lupus anticoagulant and anticardiolipin antibody levels in unselected women with a history of two or more first trimester miscarriages. The prepregnancy clinic and miscarriage antenatal clinic in a tertiary referral centre. Two hundred and forty-three women, of whom 113 (47%) had a past history of two miscarriages, and 130 (53%) had three or more miscarriages. Quantitative detection of lupus anticoagulant and anticardiolipin antibodies; number of miscarriages in women in the normal and the abnormal groups. Of the 243 women tested, 41 (16.8%) had an abnormality of lupus anticoagulant or anticardiolipin antibodies. This was significantly different from the normal population as previously reported. Sixteen women (6.6%) were positive for lupus anticoagulant, 20 (8.2%) had elevated anticardiolipin antibodies, and five (2%) had both abnormalities. The most frequently positive test for lupus anticoagulant was the dilute Russel viper venom time, and IgG was the most frequently elevated anticardiolipin antibody. Of the women with a history of only two miscarriages, 15% had an abnormality of lupus anticoagulant or anticardiolipin antibodies, compared with 18.5% of those with a history of three or more miscarriages. This did not reach statistical significance. There were 117 (48%) primary miscarriers and 126 (52%) secondary miscarriers. Of the primary miscarriers, 17% had an abnormality, compared to 18% of the secondary miscarriers. These findings provide further evidence of an association between lupus anticoagulant and anticardiolipin antibodies and early pregnancy loss. It is not known if these are the cause of miscarriage, markers for miscarriage, or if antiphospholipid antibodies develop as a result of a noncontinuing pregnancy. Further studies comparing various treatments are required before women with these antibodies can be optimally managed.

Lupus and pregnancy

Of live births, approximately one third are delivered prematurely. Miscarriage Lupus causes an increased rate of fetal death in utero and spontaneous abortion (miscarriage). The overall live-birth rate in somebody with lupus has been estimated to be 72%. Pregnancy outcome appears to be worse in those with lupus whose disease flares up during pregnancy. Miscarriages in the first trimester appear either to have no known cause or to be associated with signs of active lupus. Later losses appear to occur primarily due to the antiphospholipid syndrome, in spite of treatment with heparin and aspirin. All women with lupus, even those without previous history of miscarriage, are recommended to be screened for antiphospholipid antibodies, both the lupus anticoagulant (the RVVT and sensitive PTT are the best screening battery) and anticardiolipin antibodies.

[A case of antiphospholipid antibody syndrome successfully treated with prednisolone and low-dose aspirin, with subsequent normal pregnancy].

We reported a 26-year-old female who had experienced 2 miscarriages associated with a possible cause of antiphospholipid antibody. She consulted to Kainan Municipal Hospital with major complaints of miscarriages and positive antiphospholipid antibody. No evidence of obstetric disorder was apparent and routine haematological parameters were normal. Serological studies and clinical evidence did not show SLE. While biologically false positive (reaction of serological test for syphilis) and lupus anticoagulant was negative, IgG anticardiolipin antibody was positive. She was diagnosed as possible antiphospholipid antibody syndrome based on positive anticardiolipin antibody and the history of miscarriages. In 1993, she was started on prednisolone and aspirin therapy; antiphospholipid antibody returned to negative. Treatment with prednisolone (7.5 mg/day) and aspirin (40 mg/day) was continued. She was able to be pregnant. She gave birth successfully at our hospital in August 1995. She and her newborn showed no abnormalities.

Antiphospholipid syndrome

Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. The diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, or anti-cardiolipin antibodies.

Spontaneous first trimester miscarriage rates per woman among parous women with 1 or more pregnancies of 24 weeks or more.

The purpose of this study was to quantify spontaneous first trimester miscarriage rates per woman among parous women. A vast amount of data has accumulated regarding miscarriage rates per recognized pregnancy as well as about recurrent miscarriage. This is the second study of miscarriage rates per woman in a parous population and the first study of recurrent and non-recurrent, spontaneous first trimester miscarriage rates per woman in a large parous population. Extraction of the following variables from all delivery room admissions from both Hadassah Medical Centers in Jerusalem Israel, 2004-2014: # of first trimester spontaneous miscarriages, # live births; # living children; age on admission, pre-pregnancy height and weight, any smoking this pregnancy, any alcohol or drug abuse this pregnancy, blood type, history of ectopic pregnancy, history of cesarean surgery (CS) and use of any fertility treatment(s). Among 53,479 different women admitted to labor and delivery ward, 43% of women reported having had 1 or more first trimester spontaneous miscarriages; 27% reported having had one, 10% two, 4% three, 1.3% four, 0.6% five and 0.05% reported having 6-16 spontaneous first trimester miscarriages. 18.5% had one or more first trimester miscarriages before their first live birth. Eighty-one percent of women with 11 or more living children experienced one or more first trimester miscarriages. First trimester miscarriage rates rose with increasing age, increasing parity, after previous ectopic pregnancy, after previous cesarean surgery, with any smoking during pregnancy and pre-pregnancy BMI ≥30. Miscarriages are common among parous women; 43% of parous women report having experienced one or more first trimester spontaneous miscarriages, rising to 81% among women with 11 or more living children. One in every 17 parous women have three or more miscarriages. Depending on her health, nutrition and lifestyle choices, even a 39 year old parous woman with a history of 3 or more miscarriages has a good chance of carrying a future pregnancy to term but she should act expediently.

Ultrasonographic detection of a live fetus in recurrent spontaneous abortion during the first trimester.

To examine whether recurrent spontaneous abortion (RSA) can be distinguished from repeated sporadic spontaneous abortion, the clinical course of 38 cases with three or more consecutive and unexplained first trimester RSAs were retrospectively investigated in this study. For comparison with controls, the clinical course was examined of 38 fertile females, who had had sporadic abortions. In 19 (50%) RSAs and 6 (16%) controls, fetal cardiac activity was demonstrated by ultrasound during the course of pregnancy. The rate of detection of live fetus during pregnancy or at 8 weeks +/- 7 days gestation, was significantly greater in the RSA group compared to the control. The rate of vaginal bleeding before spontaneous abortion was significantly less in the RSA group than in the control group. There was no difference between the two groups in age or gestational age at spontaneous abortion. The patients with RSA were all examined for antiphospholipid antibodies in their sera and these were detected in eight of them. However, there was no difference in the rate of positive fetal cardiac activity between the RSA patients who tested positive or negative for antibody. These results reveal that the clinical course of RSA is very different from the course of sporadic abortion. Although sporadic abortion is a common complication of pregnancy, RSA is not a random repeated abortion, but rather a separate disease from sporadic abortion in normal fertile females.

Placenta increta presenting with threatened miscarriage during the first trimester in rhesus-negative mother: a case report.

Placenta accreta is known to be associated with significant maternal morbidity and mortality-primarily due to intractable bleeding during abortion or delivery at any level of gestation. The complications could be reduced if placenta accreta is suspected in a patient with a history of previous cesarean delivery and the gestational sac/placenta is located at the lower part of the uterus. Then, a proper management plan can be instituted, and complications can be reduced. The diagnosis of placenta accreta in the first trimester of pregnancy is considered uncommon. A 34-year-old Malay, gravida 4, para 3, rhesus-negative woman was referred from a private hospital at 13 weeks owing to accreta suspicion for further management. She has a history of three previous lower-segment cesarean sections. She also had per vaginal bleeding in the early first trimester, which is considered to indicate threatened miscarriage. Transabdominal ultrasound revealed features consistent with placenta accreta spectrum. She was counseled for open laparotomy and hysterectomy because of potential major complication if she continued with the pregnancy. Histopathological examination revealed placenta increta. A high index of suspicion of placenta previa accreta must be in practice in a patient with a history of previous cesarean deliveries and low-lying placenta upon ultrasound examination during early gestation.

A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss.

In this study the efficacy and safety of calcium heparin administered alone for the prevention of fetal loss related to antiphospholipid antibodies (aPL) were evaluated. Fifty-three consecutively ascertained pregnancies were followed in 53 patients who had a history of at least 2 consecutive miscarriages during the first trimester and/or 1 fetal death during the second or third trimesters. In addition, all patients had at least 2 positive aPL tests more than 8 weeks apart before pregnancy, or a positive aPL test at the beginning of pregnancy. They were treated with calcium heparin alone, self-administered subcutaneously 3 times daily at dosages varying between 15,000 and 37,500 units. Treatment was started soon after a sonogram demonstrated a live embryo and was continued throughout pregnancy until the end of puerperium. All pregnancies terminated favourably between the 25th and 40th weeks (mean +/- SD: 36.69 +/- 2.91) with planned caesarean section in 27 cases and vaginal delivery in 26. Delivery was brought forward due to maternal and/or fetal complications in 18 cases (33.96%). Calcium heparin was associated with intravenous immunoglobulin therapy in 2 patients with fetal problems unresponsive to anticoagulant treatment alone. The newborns, 30 females and 25 males, had a mean birth weight of 2,828.3 g +/- 706.5 and a mean Apgar score at 5 minutes of 9.60 +/- 0.68. No malformations were observed. Thirty of the 37 examined placentas (81.08%) showed signs of thrombotic events. Only minor side effects of calcium heparin were observed during treatment. Our study suggests that calcium heparin administered alone using the dosages and timing described here is effective in achieving the delivery of viable infants, and that it is well tolerated.

Higher levels of procoagulant microparticles in women with recurrent miscarriage are not associated with antiphospholipid antibodies.

Are the levels of circulating cell-derived microparticles (cMPs) in patients with recurrent miscarriage (RM) associated with the antiphospholipid syndrome (APS)? cMPs in women with RM are not associated with antiphospholipid antibodies (aPLs). Previous studies have focused on cMP levels in RM patients. Most studies have shown higher levels of cMPs in RM patients whereas others have reported lower levels. Data regarding cMPs in patients with the APS are scanty in the literature. A case-control study including three groups of patients. A total of 154 women were prospectively recruited from September 2009 to October 2013. Four patients refused to participate. The APS group consisted of 50 women that had been previously diagnosed with primary APS and had had ≥3 consecutive first trimester miscarriages. The uRM group included 52 couples with ≥3 consecutive first trimester miscarriages of unknown etiology. The fertile control (FER) group was composed of 52 healthy fertile women with no history of pregnancy losses. Miscarriage was defined as intrauterine pregnancy loss at <10 weeks' size on ultrasound. Venous blood samples for coagulation studies and cMP determinations were obtained. All patients underwent a thrombophilia study. cMP levels were significantly higher in the APS and uRM groups versus the FER group (P < 0.0001 and P = 0.009, respectively) (cMP number × 10(3)/ml plasma [mean ± SD]: APS: 18.5 ± 13.6; uRM: 16.3 ± 13.8; FER: 9.7 ± 4.6). There were no statistically significant differences in cMP levels between the APS and uRM groups. The sample size was arbitrarily decided according to previous studies analyzing cMPs in RM patients. Different cMP subtypes were not investigated. The present study adds further data on the subject showing that patients with RM, irrespective of testing positive for aPLs, have increased levels of cMPs compared with healthy fertile controls. The presence of elevated cMPs in RM women may reflect an ongoing systemic pathological, albeit asymptomatic, status that can become deleterious in the setting of pregnancy. This study was supported in part by grant from FIS-PI11/01560 within the 'Plan Nacional de I+D+I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and the 'Fondo Europeo de Desarrollo Regional (FEDER)'. The authors have no competing interests to disclose. Not applicable.

Antiphospholipid syndrome and second- or third-trimester fetal death: follow-up in the next pregnancy.

To evaluate the efficacy of a uniform management protocol in antiphospholipid-antibody-positive obstetric patients with at least one second- or third-trimester intra-uterine fetal death. A prospective study of 33 successive pregnancies in antiphospholipid-antibody-positive patients, diagnosed after an intra-uterine fetal death. The management included treatment by a combination of aspirin and low-molecular-weight heparin, and a close follow-up with at least clinical examination, ultrasonography, uterine, and umbilical artery Doppler monthly from the first trimester. In the absence of any anomaly, delivery was induced between 37 and 38 weeks' gestation. In this high risk population, seven recurrences of vascular pathology occurred: five cases of mild, isolated fetal growth retardation and one of preeclampsia associated with fetal growth retardation requiring preterm delivery. Eight patients were delivered before 37 weeks. No recurrence of second- or third-trimester fetal death was observed. Uterine artery Doppler was informative as early as the first trimester (12-15 weeks): a bilateral notch was associated with a lower birthweight (2626+/-688 g versus 3178+/-353 g, respectively, p = 0.01), despite similar gestational age. The negative predictive value of uterine Doppler was more than 92% at 12-15 weeks' gestation and remained high throughout pregnancy. Although intra-uterine fetal death is considered at high risk of recurrence in case of antiphospholipid syndrome (APS), a uniform management protocol including aspirin and heparin and close obstetrical follow-up led to a favorable outcome in most cases.

Antiphospholipid syndrome

Signs and symptoms The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS). Antiphospholipid syndrome can cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. In pregnant women affected by APS, there is an increased risk of recurrent miscarriage, intrauterine growth restriction, and preterm birth. A frequent cause of such complications is placental infarctions. In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.

High-level mosaicism for 45,X in 45,X/46,XX at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line.

We present prenatal diagnosis of high-level mosaicism for 45,X in 45,X/46,XX at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line. A 32-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of the abnormal first-trimester maternal serum screening result indicating a 1/34 risk for Down syndrome. Amniocentesis revealed a karyotype of 45,X[27]/46,XX[15]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed 12% mosaicism for monosomy X. Prenatal ultrasound was normal. The pregnancy was carried to term, and a 2780-g phenotypically normal female baby was delivered. The cord blood had a karyotype of 45,X[12]/46,XX[28]. At age one month, the peripheral blood had a karyotype of 45,X[13]/46,XX[27]. Interphase fluorescence in situ hybridization (FISH) analysis on the buccal mucosal cells revealed 2% (2/102 cells) mosaicism for monosomy X, compared with 1% (1/100 cells) in the normal control. When follow-up at age one year, she was doing well with normal physical and psychomotor development. Her body weight was 9.9 Kg (50th - 85th centile), and her body height was 75 cm (50th - 85th centile). The peripheral blood had a karyotype of 45,X[4]/46,XY[36]. High-level mosaicism for 45,X in 45,X/46,XX at amniocentesis can be associated with a favorable outcome and postnatal progressive decrease of the 45,X cell line.

Gynecology_Novak

For a patient to be diagnosed with antiphospholipid antibody syndrome, one or more clinical and one or more laboratory criteria must be present: 1. One or more confirmed episode of vascular thrombosis of any type: Venous Arterial Small vessel 2. Pregnancy complications: of gestation with exclusion of maternal anatomic and hormonal abnormalities and exclusion of paternal and maternal chromosomal abnormalities One or more unexplained deaths of a morphologically normal fetus at or beyond 10 weeks of gestation (normal fetal morphology documented by ultra sound or direct examination of the fetus) One or more premature births of a morphologically normal neonate at or before 34 weeks of gestation secondary to severe preeclampsia or placental insufficiency Testing must be positive on two or more occasions with evaluations 12 or more weeks apart: 1. Positive plasma levels of anticardiolipin antibodies of the IgG or IgM isotype at medium to high levels 2.

A case of incidental endometrial adenocarcinoma diagnosed in early pregnancy and managed conservatively.

We report a 29-year old nulliparous woman diagnosed with a grade 1 endometrioid adenocarcinoma of the endometrium arising from an atypical polypoid adenomyoma, while being investigated for a suspected threatened miscarriage at 7 weeks gestation. She presented complaining of vaginal bleeding and a small amount of soft tissue in the cervical os was found and sent for histology. An ultrasound scan was performed, which confirmed an intrauterine ongoing pregnancy. The patient had no further episodes of unscheduled bleeding. After the confirmed histological diagnosis an MRI scan was requested, and there were no evidence of myometrial invasion or distant metastasis. The patient was seen at each trimester, remained asymptomatic throughout the pregnancy and had a normal delivery at term. There was no evidence of any residual endometrioid adenocarcinoma in the post-delivery specimen. Six weeks post-natally an endometrial biopsy was performed, which was normal. She is still in remission over a period of 8 years follow-up. Endometrial adenocarcinoma in young pregnant women is a rare clinical circumstance. This case shows that conservative management in young women is possible including in a case of an incidental diagnosis in pregnancy.

Two miscarriages, consecutive or non-consecutive, does it change something?

To assess the rate of anomalies in the etiological evaluation of patients presenting recurrent early miscarriages (RM) according to miscarriage chronology (number of miscarriages, history of live birth and succession of RM). Retrospective single centre study including RM, defined as at least 2 miscarriages at less than 14 weeks of gestation (WG) between the 1st January 2012 and the 31st December 2015. Clinical data and etiological evaluation include blood glucose levels, screening for antiphospholipid syndrome (APS), endocrine assessment, vitamin levels, pelvic imaging, karyotyping of both partners, chronic endometritis and thrombophilia screening. Two hundred and eighty-eight patients were included over this period, 118 (41%) patients had no history of live birth. Two hundred and twenty-three (77%) patients had consecutive RM and 65 (22%) patients had non-consecutive RM. For consecutive RM, 62,8% had thrombophilic disorders versus 69,8% for non-consecutive RM (P>0,05); 44,7% had endocrine disorders or vitamin deficiencies versus 39,7%; 34,6% of patients with consecutive RM had uterine anomalies versus 45,5% respectively. No difference was found depending on the recurrence of RM or the history of live birth (P>0.05) apart from the age of the patient. Fifty-nine (17.4%) patients had uterine anomalies. There are 24 chronic endometritis on 31 biospsies performed. Seventy-eight (27%) patients were offered treatment. Ninety-four (90%) patients showed good therapy compliance. Eighty-one (78%) patients became pregnant. An etiological evaluation provides, for over half of the cases, an etiology or the identification of risk factors responsible for RM, as well as in some cases offering an adapted, efficient, therapeutic approach. This evaluation should be offered regardless of the obstetric history of the patient.

Autoimmune diseases and pregnancy: analysis of a series of cases.

An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid function over the years and first trimester miscarriage, suffered a second miscarriage despite clinical stability and antibody regression. As described in literature, the authors found a strong association between autoimmune disease and obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome and autoimmune thyroiditis.

Complement as a predictor of further miscarriage in couples with recurrent miscarriages.

The clinical significance of complement is unclear in patients with unexplained recurrent miscarriage, though low levels of complement 3 (C3) and/or complement 4 (C4) are reported to be associated with the antiphospholipid syndrome (aPS). We therefore investigated whether C3 and C4 have a predictive value for subsequent miscarriages. In total, 215 patients with a history of two consecutive first-trimester miscarriages and no abnormal chromosomes in either partner, no uterine anomalies and no antiphospholipid (aPL) antibodies were examined. Blood tests for C3, C4, total haemolytic complement (CH50), immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were performed before subsequent pregnancy. Patients were then followed up without treatment, and their pregnancy outcomes were compared with their previous blood test results. From 215 pregnant patients, 45 subsequently miscarried, whereas the remainder had a live birth. There was no relation with serum CH50, IgG, IgA and IgM levels, but C3 and C4 levels in patients with subsequent miscarriage were significantly higher than in those whose pregnancy was successful. In patients with two previous miscarriages, C3 and C4 levels were higher in those women who had a third miscarriage, than in women that went on to have a live birth.

[Comparison of the etiological constitution of two and three or more recurrent miscarriage].

<bObjective:</b To compare the etiological constitution of recurrent miscarriage (RM) between patients with consecutive two and three or more miscarriages through combining the routine examination results and embryonic karyotype. <bMethods:</b Patients with a history of two or more consecutive clinical miscarriages (≤12 weeks of gestation) consulting in the RM clinic of the First Affiliated Hospital of Sun Yat-sen University from March 2011 to January 2016 were collected. Six hundred and ninety-six with detailed history recorded, routine clinical examinations of RM and at least once embryonic karyotype were ultimately enrolled in this study. Their etiological constitution of RM were analyzed in groups of consecutive two and three or more miscarriage. The etiologies of RM in analysis consisted of women age, body mass index (BMI) , chromosome abnormalities of couples, uterine abnormalities, endocrinology abnormalities and antiphospholipid syndrome (APS) . <bResults:</b (1) Among 696 patients, the abnormal embryonic karyotypes was 60.6% (422/696) and routine RM etiologies was 32.2% (224/696) , leaving the ratio of unexplained RM was only 29.0% (202/696). (2) A total of 717 embryo karyotype were found in 696 patients, included21 cases with twice embryo karyotype results the percentage of normal embryo was 39.7% (285/717) , while abnormal ones was 60.3% (432/717). Among the types of abnormal karyotype, the most common ones (>10%) were trisomy 16 (19.2%, 83/432) , monosome X (11.3%, 49/432) and trisomy 22 (10.9%, 47/432). (3) Among the 696 RM patients, the number of two and three or more miscarriages were respectively 446 (64.1%, 446/696) and 250 (35.9%, 250/696). Comparing groups of three or more miscarriages with two miscarriages, there were significant differencein older age as well as uterine adhesion (<iP<</i0.05). But no difference was found in body mass index (BMI) , the rates of chromosome abnormalities of couples, uterine abnormalities except uterine adhesion, endocrinology abnormalities and APS (all <iP></i0.05) between two groups. <bConclusions:</b The abnormal embryonic karyotype is the most common cause of first-trimester RM. The etiological constitution of two and three or more recurrent miscarriages is accordant, suggesting that routine clinical examination and the embryonic karyotype should be started following two consecutive clinical early miscarriages.

Trisomy 20 mosaicism and nonmosaic trisomy 20: a report of 2 cases.

Together with chromosome 19, chromosome 20 belongs to group F, the group of small metacentric chromosomes. Trisomy 20 mosaicism is one of the most frequent chromosomal mosaicisms, representing approximately 16% of prenatally diagnosed cases. In nonmosaic trisomy 20, the usual findings are severe and manifold. Only 3 cases in the literature involved fetuses surviving past the first trimester. In case 1, a 42-year-old woman presented in her sixth pregnancy; she had had 4 vaginal deliveries of term infants and a miscarriage. Both her familial and personal genetic histories were unremarkable. Genetic amniocentesis was performed in the 18th gestational week for advanced maternal age. Sample analysis revealed a normal, male karyotype in 27 mitoses, while 4 were trisomy 20 (46,XY [27]/47,XY, +20 [4]). In the 37th gestational week a live, immature, male infant weighing 1,730 g was delivered. Chromosomal investigation of the newborn's blood sample did not reveal trisomy 20 but a normal male karyotype. In case 2, a healthy 37-year-old nullipara underwent amniocentesis at the 18th week of pregnancy for advanced maternal age. Amniotic fluid cell karyotype revealed trisomy 20 (47,XX, +20). Ultrasonography performed simultaneously with genetic amniocentesis showed slightly shortened fetal long bones, detectable narrowing of the cranium in the region of the frontal bone, lateral ventricles of 10 mm in width bilaterally, echogenic bowel and polyhydramnios. Abortion was induced in the 23rd week of pregnancy, and a 490-g female fetus was delivered. Based on these 2 well-documented, prenatally diagnosed cases, as far as genetic counseling is concerned, nonmosaic trisomy 20 is much less challenging than its mosaic form since the prognosis is uniformly poor in the former.

Pre-eclampsia with new-onset systemic lupus erythematosus during pregnancy: A case report.

New-onset systemic lupus erythematosus (SLE) during pregnancy and in the postpartum period is rare, especially when complicated with pre-eclampsia, which is difficult to diagnose accurately. Here, we report a patient with new-onset SLE and antiphospholipid syndrome during pregnancy, which presented as pre-eclampsia at admission. A 28-year-old primigravid woman was admitted to our hospital in the 27<supth</sup wk of gestation with the primary diagnosis of severe pre-eclampsia. Although spasmolysis and antihypertensive therapy were administered since admission, the 24-h proteinuria of the 2nd day after admission reached 10311.0 mg. In the 47<supth</sup h of admission, immunologic examinations revealed increased levels of anti-double stranded DNA antibody, anti-nuclear antibody, anti-cardiolipin antibody, anti-Sjögren's syndrome-related antigen A antibody and anti-nucleosome antibody and decreased levels of complement C3 and C4. One hour later, ultrasonography of the lower limbs showed thrombus of the bilateral popliteal veins. The diagnosis of SLE and antiphospholipid syndrome was indicated. In the 54<supth</sup h, the patient manifested with convulsion, dyspnea and blurred vision. Ten hours later, intrauterine death was revealed by ultrasonography. Emergent surgery consisting of inferior vena cava filter implantation and subsequent cesarean section was performed. Following glucocorticoid and anticoagulation therapy after delivery, the patient had an optimal response with improvements in symptoms and immunological markers. Obstetricians should be aware of the symptoms and immunological examination results to distinguish pre-eclampsia and underlying SLE for optimal pregnancy outcomes.

First-trimester miscarriage in the background of endometrial carcinoma.

Endometrial cancer in young women (less than 40-year-old) is associated with anovulatory menses, polycystic ovarian syndrome (PCOS) and subfertility. Endometrial cancer occurring in a miscarriage is rare. We highlight a case of endometrial cancer occurring during miscarriage of a non-viable pregnancy, its management and the outcome. A 32-year-old woman, Gravida 1 Para 0, was referred to our center at 7 weeks gestation in 2018 for uncontrolled diabetes mellitus diagnosed during investigation for subfertility. Her poor compliance with the treatment is consistent with an HbA1c of 8%. During the assessment, she was already complaining of lower abdominal pain. Ultrasound showed irregular IUGS with no fetal echo. She had a miscarriage soon; however, due to ultrasound evidence of thickened and irregular endometrium (17 mm) with mixed echogenicity, dilatation and curettage (D + C) were commenced. The first and second tissues were reported as the product of conception (POC) and well differentiated endometrioid adenocarcinoma, respectively. The first hysteroscopy showed foci area of polypoidal growth at the right posterior endometrium, obscuring the right ostium, with similar histology report. She was commenced on high-dose progestogen with hysteroscopy surveillance 6 months later, which showed disease regression. After two normal hysteroscopies and endometrial biopsies with continuous progestogen therapy for 12 months, cyclical progestogen for 12 months and follow-up for another 6 months, she had spontaneous conception and is currently pregnant at 16 weeks gestation. Endometrial cancer should be suspected in high-risk patients with first-trimester miscarriage. Individualized treatment with high dose progestogen and follow-up with the proper patient and partner counselling and education has high successful regressionand later on, pregnancy rate.

Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses.

To determine whether the frequency of abnormal results for evidence-based diagnostic tests differed among women with recurrent pregnancy loss (RPL) based on the number of prior losses (n = 2, 3, or > or =4) and to determine whether abnormal results for additional investigative diagnostic tests differed in prevalence among women with different numbers of pregnancy losses. Single-center, retrospective study. Patients with RPL at a private practice. One thousand twenty women who had two or more consecutive spontaneous pregnancy losses with the same partner. None. Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities; pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; thrombophilic tests for the factor V Leiden mutation; and blood tests for thyroid-stimulating hormone [TSH] and fasting blood glucose). We also measured the frequency of abnormal results for nine additional investigative tests in the same patients (antiphosphatidyl serine antibodies, microbial infection, midluteal P, PRL, functional protein C activity, functional protein S activity, antithrombin activity, fasting homocysteine and methylenetetrahydrofolate reductase polymorphisms, and factor II mutation). The prevalence of abnormal results for evidence-based and investigative diagnostic tests did not differ among women with different numbers of pregnancy losses. Evaluation of all couples with two, three, or more consecutive miscarriages is recommended.

[Clinical analysis of eleven patients with chronic myeloproliferative disorders complicating pregnancy].

To investigate the clinical characteristics, the antenatal management, the outcome and prognosis of chronic myeloproliferative disorders(CMPD) complicating pregnancy. Retrospectively analyze the clinical data of eleven patients with CMPD complicating pregnancy hospitalized in Peking University People's Hospital from 2000 to 2009, including five patients with essential thrombocythemia, one with primary myelofibrosis and five with chronic myeloid leukemia. (1) Five pregnancies had periodic antenatal care and laboratory monitorings like full blood count. Reasonable anti-coagulation therapy was given to prevent the complications. One patient with PMF diagnosed before conception had her first pregnancy ended with mild pre-eclampsia and intrauterine death at the gestational age of 32 weeks. During the first trimester of her second pregnancy two years later, the test for anti-β2 glycoprotein antibody was positive. She received low-dose aspirin and low-molecular-weight heparin as anti-coagulants. An uneventful course was obtained and she delivered a healthy term infant. (2) Five pregnancies had occasional antenatal examination, including two patients with ET and three patients with CML. One patient with ET developed severe pre-eclampsia at the gestational age of 25 weeks. Umbilical artery Doppler showed reversed end-diastolic velocity. The management with anti-convulsants, anti-hypertensives and anti-coagulants showed no effect. An emergency cesarean section had to be performed because of the aggressive hypertension and placental abruption, with still birth as a result. Two pregnancies never had an antenatal care. Both of them were admitted on labor and the diagnoses of CML were made. (3) Four pregnancies developed oligohydramnios and three developed preelampsia (two severe pre-eclampsia and one mild pre-eclampsia). There was no other hemorrhage and thrombosis event. (4) Eight pregnancies reached full-term with four cesarean sections and four vaginal births. Two preterm cesarean sections were performed because of a progressive oligohydramnios. The ten live neonates weighed 1820 - 3600 g. All were appropriate for gestational age, except one fetal growth retardation (FGR) developed in one patient with severe pre-eclampsia. (5) As for the CMPD, the eleven patients were all in stable conditions. Three patients with CML received hydroxyurea in the third trimester, four with ET and one with CML had platelet-pheresis before delivery with favorable effect. All patients were uneventful postpartum, except one with CML who died in 5 months after childbirth. The pregnancy outcomes for patients with CMPD are mostly good. However, antenatal care should pay more attention to the complications such as thromboembolic accidents, pre-eclampsia, still birth and fetal growth retardation. Management including reasonable anti-coagulation therapy should be considered, which may help improve the prognosis.

Second Tunisian case of Anti -Tja mediated recurrent abortions.

The diagnosis and the treatment of rare phenotypes remain a problematic situation in many countries especially in Tunisia. Individuals with rare phenotype may develop clinically significant red cell antibodies directed against the high incidence Antigens they lack. A 35 years old patient was referred to our laboratory to explain a high incidence (twelve) of recurrent miscarriage during the first and second terms of pregnancy. This patient was grouped as O Rhesus: 1, -2, -3, 4, 5 K:-1. In her plasma we identified a pan-reactive anti-PP1PK antibody (anti-Tja) recognized to be responsible of spontaneous recurrent abortions. The red cell phenotype was P1 and Tja negative. More investigations concluded to the absence of auto and other allo-antibodies association. Therapeutic plasmapheresis from early stages was suggested for the future pregnancy to remove anti-public antibodies in order to maintain normal placenta functions. The Anti-Tja antibody, naturally occurring in patients with rare p phenotype, has the ability to induce recurrent spontaneous miscarriages and to cause immediate hemolytic transfusion reactions. Despite the absence of compatible donors in her family, this patient is not in an impasse situation because two donors with the same phenotype were identified when investigating a first case in 2013.

[Endometriosis with massive hemorrhagic ascites: a case report and review of the literature].

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. It generally involves the peritoneum, ovaries and rectovaginal septum. Its characteristic symptoms include dysmenorrhea, pelvic pain, deep dyspareunia and infertility. It may also involve the gastrointestinal tract, urinary tract or extra abdominal sites, giving rise to a wide variety of clinical symptoms such as bloody stools, renal haemorrhage, hemoptysis and pleural effusion during menstruation. Recurrent hemorrhagic ascites secondary to endometriosis is an unusual occurrence, 41 cases have been reported since 1954. Here we report an additional case, in order to draw attention to this condition. A 28 years-old black nulligravida woman was seen for the first time in april 2000 with a chief complaint of infertility. Her past medical history was unremarkable. She had regular menses but associated with severe dysmenorrhea. She also recalled abdominal and pelvic pain for several years. She underwent an ovulation induction with gonadotrophin, which resulted in a progressive increase of pelvic pain. A first laparoscopy was performed, revealing voluminous ascites (10 I). Two years later the ascites recurred spontaneously. Ultrasound examination revealed suspect "para uterine masses". A second exploratory laparoscopy showed a voluminous bloody ascites (71), and extensive adhesions. On histologic examination all specimens (peritoneal biopsies) were compatible with endometriosis and ruled out malignancy. Treatment with Gn RH analog was performed and full remission was obtained after 6 months. One year later the ascites recurred again spontaneously, leading to a third laparoscopy in an other medical institution. Histologic examination showed endometrial stromal tissue and fibrous proliferation. Later she became pregnant after in vitro fertilization. In the first trimester of pregnancy, the pelvic ultrasound showed only a small effusion in the pouch of Douglas. Still, the ascites did not progress during pregnancy. The patient was hospitalized from 27 to 33 weeks of gestational age for threatened labor, but she finally had a normal vaginal delivery at 36 weeks of gestational age. Four months later, she had no complaint, but the pelvic ultrasound showed the recurrence of the ascites. She will have a drainage. The future treatement will consists of GnRH analog for about six months, which will be relayed by a long term progestative therapy. A diagnosis of endometriosis should always be considered in middle-age women who presents with bloody ascites. Long follow-up is advisable for patients who undergo conservative treatment because of thehigh risk of recurrence.

Pregnancy-triggered antiphospholipid syndrome in a patient with multiple late miscarriages.

Antiphospholipid syndrome (APS) is a multisystemic disorder of coagulation-causing thrombosis in the arterial and venous system as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery and pre-eclampsia. The disease is characterized by the autoimmune production of antibodies against phospholipid, a substance found in the cell membrane. We here report the case of a patient with four second trimester miscarriages, who apart from a heterozygous plasminogen activator-inhibitor-1 mutation, had no risk factors explaining her condition. In the subsequent pregnancy she was therefore put on low-molecular-weight heparin, aspirin and granulocyte colony-stimulating factor. Antiphospholipid antibodies (APL), which had been negative before gestation, increased and remained high throughout pregnancy, thus suggesting a pregnancy-induced or -aggravated APS. The patient was kept on the above-mentioned medication and delivered a healthy male baby by Caesarean section after an otherwise uneventful pregnancy. Thus, in order to diagnose and treat pregnancy-triggered APS in patients with unexplained recurrent miscarriage, screening for APL should also be performed at several time points after conception.

Concurrent ruptured spontaneous heterotopic pregnancy and ruptured appendix with delayed presentation in the first trimester: a case report.

Acute appendicitis is the commonest non-gynaecological surgical emergency in pregnancy. However, the concurrent occurrence of acute appendicitis with a heterotopic pregnancy is a rare event and presents diagnostic challenges to unsuspecting clinicians and sonographers. We present a case of a woman who had a heterotopic pregnancy and was noted to have a gangrenous appendicitis at laparotomy, illustrating how a diagnosis of acute appendicitis could easily be missed in pregnancy. We report the case of a 34-year-old woman in the first trimester of pregnancy who had a missed diagnosis of acute appendicitis after she had complained of vague abdominal symptoms for three weeks. She presented to a gynaecologist with vaginal bleeding for three days and was noted to have a heterotopic pregnancy on ultrasound scan. At laparotomy, she was noted to have a gangrenous appendicitis with pyoperitoneum concurrent with a ruptured left fimbrial ectopic pregnancy. Left salpingectomy and saline lavage were done and she had uneventful post-operative recovery. Unsuspecting clinicians, in patients without risk factors, can miss both heterotopic pregnancy and acute appendicitis. As assisted reproductive techniques become widespread, the possibility of heterotopic pregnancies must always be considered and any patient who presents with vague abdominal symptoms must be suspected to have the possibility of acute appendicitis. Because of the unreliability of laboratory investigations and clinical predictive scores in pregnancy, sonographers must be specifically asked to scan for heterotopic pregnancy and appendicitis in suspected cases.

A report of three consecutive pregnancies in a kidney transplant recipient and the challenges in their management in a poor resource setting.

Kidney transplant recipients (KTR) have a good outcome of pregnancies. However the mother and the child are increasingly at higher risks of complications compared to the general population. The management of these pregnancies is associated with greater challenges and is better if managed by both the obstetrician and the transplant physician. Kidney transplant is available in few centres in Nigeria and the post transplant population is increasing, but to our knowledge no report on pregnancy management in KTR has been published. We present a 25 years old Nigerian who had a live related kidney transplant and later had 3 consecutive pregnancies and review the relevant literature. She was placed on oral contraceptive pills for 2 years after transplantation. She enjoyed a stable allograft function with no rejection episode, no proteinuria, had a good blood pressure control and pelvic ultrasound scan was essentially normal. She conceived her first pregnancy 26 months post transplant however she developed spontaneous abortion at 3 months gestation. She conceived her second pregnancy 33 months post transplant which was supervised by the obstetrician and the transplant physician. She had complications including urinary tract infection, anaemia and dyslipidaemia and delivered a live baby girl weighing 2.4 Kg by spontaneous vaginal delivery at 36 weeks gestation. She conceived her 3rd pregnancy 8 months later which was also carried to term and had a vaginal delivery of a live baby girl weighing 2.55 kg. This report highlights the successful management of pregnancies in KTR and the challenges faced in a poor resource setting.

First-trimester bleeding and the vanishing twin. A report of three cases.

Ultrasonic examination of early pregnancies can lead to the discovery of vanishing twins. The main reason for such an evaluation is bleeding in the first trimester. Three women came to the emergency room of a community hospital with pelvic cramps and significant uterine bleeding containing clots. In two cases the cervix was soft and dilated, but in no case was the uterus smaller than was appropriate for the gestational age. Ultrasonic evaluation revealed a set of twins in all three patients. Patient 1 experienced early disappearance of a gestational sac (before ten weeks). Ultrasound demonstrated a blighted ovum in patient 2 until the 24th week of pregnancy. Macroscopic examination of patient 2's placenta at the birth of a normal, term, singleton infant revealed a compressed gestational sac. Patient 3 had developed a fetus papyraceous of 26 weeks' gestational size along with a normal singleton pregnancy. The only apparent complication associated with disappearance of a twin was first-trimester bleeding. Apparently a vanishing twin need not adversely affect the development of a coexisting singleton pregnancy. Therapeutic dilation and curettage for threatened or inevitable abortion should be avoided until a sonogram rules out the presence of a potentially surviving twin.