Sensitive Pregnancy Test Research Articles

Highly sensitive pregnancy test kit via oriented antibody conjugation on brush-type ligand-coated quantum beads

Lateral flow assays (LFA) enable development of portable and rapid diagnostic kits; however, their capacity to detect low levels of disease markers remains poor. Here, we report a highly sensitive pregnancy test kit as a proof of concept, by combining brush-type ligand-coated quantum beads (B-type QBs) and nanobody, which can control the antibody orientation and enhance sensitivity. The brush-type ligand provided excellent dispersion stability and high-binding capacity toward antibody. Fc-binding nanobody increased the antigen-binding capacity of conjugated antibodies on the B-type QBs. To facilitate convenient acquisition of the LFA results, we developed a smartphone-based reader with a 3D-printed optical imaging module, and validated the diagnostic performance of the sensing platform. The pregnancy test kit achieved a 5.1 pg mL−1 limit of detection, corresponding to the levels for early-stage detection of heart disease and malaria. Our LFA application can potentially be expanded to diagnosis other diseases by simply changing the antibody pair in the kit.

Abdominal intrauterine vacuum aspiration

Evaluating and “cleaning” of the uterine cavity is probably the most performed operation in women. It is done for several reasons: abortion, evaluation of irregular bleeding in premenopausal period, and postmenopausal bleeding. Abortion is undoubtedly the number one procedure with more than 44 million pregnancies terminated every year. This procedure should not be underestimated and a careful preoperative evaluation is needed. Ideally a sensitive pregnancy test should be done together with an ultrasound in order to confirm a uterine pregnancy, excluding extra-uterine pregnancy, and to detect genital and/or uterine malformations. Three out of four abortions are performed by surgical methods. Surgical methods include a sharp, blunt, and suction curettage. Suction curettage or vacuum aspiration is the preferred method. Despite the fact that it is a relative safe procedure with major complications in less than one percent of cases, it is still responsible for 13% of all maternal deaths. All the figures have not declined in the last decade. Trauma, perforation, and bleeding are a danger triage. When there is a perforation, a laparoscopy should be performed immediately, in order to detect intra-abdominal lacerations and bleeding. The bleeding should be stopped as soon as possible in order to not destabilize the patient. When there is a perforation in the uterus, this “entrance” can be used to perform the curettage. This is particularly useful if there is trauma of the isthmus and uterine wall, and it is difficult to identify the uterine canal. A curettage is a frequent performed procedure, which should not be underestimated. If there is a perforation in the uterus, then this opening can safely be used for vacuum aspiration.

Menstrual Disorders

Menstrual Disorders

On the ‘Diagnostic values of serum hCG on the outcome of pregnancy of unknown location (PUL): a systematic review and meta-analysis’

Several decades ago, women with early pregnancy complications were empirically treated with surgery, either to stop potential haemorrhage from suspected ectopic pregnancy, or to stop vaginal bleeding from ‘inevitable abortion’. This was neither reassuring for patients nor safe for mothers as we have all seen ‘inevitable abortions’ delivered at term. Thankfully, these dark ages are behind us. Today, we have sensitive urine pregnancy tests, high resolution, transvaginal ultrasound and logistic regression hCG models, whilst suspected ectopic pregnancy has been replaced by pregnancy of unknown location (PUL). The concern is that, despite all these advances, mothers and babies may still not be quite safe. In our desire to diagnose ectopic pregnancy as early as possible, we may cause harm by over-diagnosing ectopic pregnancy. False-positive diagnosis of ectopic pregnancy inevitably leads to unnecessary interventions and some normal intrauterine pregnancies being treated with methotrexate or curettage. Mothers may be subjected to ‘negative’ laparascopies, despite the fact that they suffered a miscarriage which would resolve spontaneously without any intervention. Constructing evidence-based practice from data synthesis requires careful scrutiny and critical analysis of existing literature. Precise tools applied to imprecise data do not lead to good progress. In order to make our practice safer, we need to accept that there should be zero tolerance for mistakenly diagnosing miscarriage, or ectopic pregnancy in cases where very early and viable intrauterine pregnancy exists. For any diagnostic algorithm that aims to detect normally developing intrauterine pregnancy, any false-negative results are simply unacceptable. To find out how the current hCG algorithms perform in this respect, we should turn to the systematic review by van Mello et al. Such reviews with meta-analysis are considered mandatory in the evaluation of effectiveness and safety of medical and surgical interventions, yet they are quite rare when it comes to diagnostic tests. The common excuse has been that the methodology for literature searching and data synthesis has not been robust enough for such reviews to be clinically useful, but this is no longer the case. Van Mello et al. provide a good example of methodologically robust meta-analysis which, hopefully, others in our speciality will follow. Having looked at 980 citations and 23 included study, the authors concluded that the definitions of intrauterine pregnancy were so inconsistent that meta-analysis was not possible. This may be disappointing, but is not unexpected. The same problem has been encountered in meta-analyses of interventions, time and again. The solution is simple—we need prospective studies with internationally agreed definitions and registered protocols. Cognisant of the present predicament, we need to recognize that a zero tolerance for false-negative diagnosis of normally progressing intrauterine pregnancy means that in clinically stable women with non-diagnostic ultrasound findings we should act simply to wait and watch—as long as it takes—to reach a conclusive diagnosis of intraor extrauterine pregnancy. And herein lays the dilemma. We are not really prepared to wait too long in the presence of PUL. When balancing fears of mistakenly treating intrauterine pregnancy against missing a ‘life-threatening ectopic’, the second one usually prevails. This inevitably leads to overdiagnosis of ectopic pregnancy and employment of ‘preventative’ management strategies. van Mello et al. offer an insight in the current definitions of ‘clinically important’ ectopic pregnancy that most clinicians believe is worth detecting and treating. Purists would argue that only histological confirmation of chorionic villi in a symptomatic patient should be labelled as a true ectopic pregnancy. However, in line with current thinking, van Mello et al. were compelled to accept in their meta-analysis as a ‘gold standard’ not only ectopic pregnancies confirmed histologically after laparoscopy or laparotomy, but also visual confirmation during laparoscopy without histology, hCG increase after D&C or systemic metorexate

Gynaecological causes of abdominal pain

Gynaecological causes of abdominal pain may arise from conditions associated with pregnancy and the non-pregnant state. In the former, the presentation is usually as an emergency and the most important diagnosis is ectopic pregnancy. In women who are not pregnant, the most common emergencies associated with abdominal pain are acute pelvic inflammatory disease and complications of ovarian cysts. Less acute causes of abdominal pain include endometriosis, fibroids and chronic pelvic inflammatory disease. Women with acute abdominal pain due to gynaecological disease may present to surgeons, and the most useful investigations for possible gynecological problems are sensitive pregnancy tests and pelvic ultrasonography. A negative pregnancy test effectively excludes an ongoing pregnancy. Gynaecological conditions may be encountered during surgery (particularly diagnostic laparoscopy) and gynaecologists must be involved in management decisions when a gynaecological abnormality is suspected preoperatively or if it is encountered intraoperatively. The most important cause of abdominal pain due to a gynaecological problem is ovarian cancer. This rarely presents acutely, but often gives rise to vague abdominal symptoms. The cancer has usually spread by the time of diagnosis, and clinicians should be particularly vigilant in postmenopausal women with vague abdominal symptoms.

Missed Abortion with a Coexisting Ectopic Pregnancy Encased within an Intraovarian Hematoma

An ectopic pregnancy is defined as a pregnancy following implantation of the fertilized egg on any tissue other than the mucous membrane lining the uterine cavity.The incidence of ectopic pregnancy has been on the rise since 1970.Currently, ex tremely sensitive pregnancy tests exist that allow early diagnosis of unsuspected cases of ectopics. Another method of discovery in the diagnosis of ectopic pregnancy is high-resolution endovaginal sonography.

Which Ectopic Pregnancy Treatment Is Best for Preserving Fertility

Sensitive pregnancy tests and ultrasounds allow early detection of ectopic pregnancies, enabling clinicians to use treatment techniques that may

The frequency of salpingitis and ectopic pregnancy as epidemiologic markers of Chlamydia trachomatis.

To study the incidence of non-gonococcal salpingitis, gonococcal salpingitis and ectopic pregnancy in a defined population over a 28-year period on the assumption that the frequency of salpingitis and ectopic pregnancy may indirectly illustrate the epidemiological pattern of Chlamydia trachomatis. A retrospective epidemiological study. University hospital with an urban catchment area. Five thousand two hundred and thirty-three patients admitted to the hospital between 1969 and 1996 with a diagnosis of ectopic pregnancy, non-gonococcal salpingitis, or gonococcal salpingitis. The frequencies of both non-gonococcal and gonococcal salpingitis increased steeply early in the period under study, rising to a peak in the early 1970s, then decreasing throughout the period except for the last 3 years when a slight increase was seen again. The frequency of ectopic pregnancy showed a steady increase, peaking in the late 1980s and early 1990s and then declining at the end of the study period. While the introduction of more sensitive pregnancy tests and programs for assisted fertility would increase the rate of ectopic frequency the decline during the 'nineties cannot be accounted for in this way. The peak of salpingitis cases in the early 'seventies seems to be mirrored exactly by the peak of ectopic pregnancies fifteen years later in the late 'eighties. The frequencies of salpingitis and of ectopic pregnancy can probably be used to estimate the incidence of preceding Chlamydia trachomatis. Thus the incidence of C. trachomatis has probably declined since the early 'seventies like that of N. gonorrheae.

Interventions for tubal ectopic pregnancy.

The diagnosis of ectopic pregnancy can now often be made by non-invasive methods due to sensitive pregnancy tests (in urine and serum) and high resolution transvaginal sonography, which have been integrated in diagnostic algorithms. These algorithms, in combination with the increased awareness and knowledge of risk factors among both clinicians and patients, have enabled an early and accurate diagnosis of ectopic pregnancy. As a consequence, the clinical presentation of ectopic pregnancy has changed from a life threatening disease to a more benign condition. This in turn has resulted in major changes in the options available for therapeutic management. Many treatment options are now available to the clinician in the treatment of tubal pregnancy: surgical treatment, which can be performed radically or conservatively, either laparoscopically or by an open surgical procedure; medical treatment, with a variety of drugs, that can be administered systemically and/or locally by different routes (transvaginally under sonographic guidance or under laparoscopic guidance); expectant management. The choice of a treatment modality should be based on short-term outcome measures (primary treatment success and reinterventions for clinical symptoms or persistent trophoblast) and on long-term outcome measures (tubal patency and future fertility). In the treatment of tubal pregnancy various types of treatments are available: surgical treatment, medical treatment and expectant management. In this review the effects of various treatments are summarized in terms of treatment success, need for reinterventions, tubal patency and future fertility. The Cochrane Menstrual Disorders and Subfertility Group trials register and MEDLINE were searched. Randomized controlled trials comparing treatments in women with ectopic pregnancy. Trial quality was assessed and data extracted independently by two reviewers. Differences were resolved by discussion with all reviewers. Laparoscopic conservative surgery is significantly less successful than the open surgical approach in the elimination of tubal pregnancy due to a higher persistent trophoblast rate of laparoscopic surgery. Long term follow-up shows similar tubal patency rates, whereas the number of subsequent intrauterine pregnancies is comparable, and the number of repeat ectopic pregnancies lower, although these differences are not statistically significant. The laparoscopic approach is less costly as a result of significantly less blood loss and analgesic requirement, and a shorter duration of operation time, hospital stay, and convalescence time. Compared to laparoscopic conservative surgery (salpingostomy) local methotrexate is not a treatment option. Injection of this drug, both under laparoscopic guidance and under ultrasound guidance, is significantly less successful in the elimination of tubal pregnancy. Systemic methotrexate in a single dose intramuscular regimen is not effective enough in eliminating the tubal pregnancy compared to laparoscopic salpingostomy. This as a result of inadequately declining serum hCG concentrations after one single dose of methotrexate necessitating additional methotrexate injections or surgical interventions. If methotrexate primarily given in a multiple dose intramuscular regimen is compared with laparoscopic salpingostomy no large differences are found in medical outcomes, both short term and long term. However, this treatment regimen is associated with a greater impairment of health related quality of life and is more expensive, due to surgical interventions for clinical signs of tubal rupture, generating additional direct costs due to prolonged hospital stay. Furthermore, indirect costs due to productivity loss are higher. Only in patients with low initial serum hCG concentrations systemic methotrexate leads to costs savings compared to laparoscopic salpingostomy.

Increasing incidence of ectopic pregnancy in one Norwegian county--a population based study, 1970-1993.

To estimate time trends related to ectopic pregnancy while considering the contribution of repeat ectopic pregnancy and changing treatment for infertile couples over the past 24 years. Population based incidence data on ectopic pregnancy were collected from the only two hospitals in one Norwegian county from 1970 through 1993. Cases were identified through hospital discharge registries and all medical records were reviewed. Only females, aged 15-44 years, living permanently in the county and having a histologically verified ectopic pregnancy were eligible for the study. Data were analyzed in 5-year periods and 5-year age-groups. The incidence of ectopic pregnancy (per 1,000 woman-years) increased fourfold from the first to the last period. When we restricted the analyses to women with no previous ectopic pregnancy and no previous infertility surgery or treatment, we observed a linear threefold increase in the number of ectopic pregnancies. Repeat ectopic pregnancy and increased infertility treatment in the late 1970s and early 1980s might explain at most 25% of the increase in the incidence of ectopic pregnancy. After 1985, assisted reproduction might contribute to 4-5% of ectopic pregnancies diagnosed. The introduction of laparoscopy might explain some of this increase in the 1970s; however, we doubt that the introduction of more sensitive pregnancy tests or vaginal ultrasound in the 1980s contributed to the observed increase in ectopic pregnancy.

The Value of a Single Sensitive Urine Pregnancy Test in Prediction of Pregnancy Outcome

A simple and reliable indicator for pregnancy outcome will be valuable clinically for patient management and for counselling women whose pregnancies are results of subfertility treatment. This study aimed at evaluating the ICON II test, a simple semiquantitative sensitive urine pregnancy test, in predicting pregnancy outcome in women who conceived after various forms of subfertility treatment. The ICON II test was performed on day 20 after the ovulating dose of hCG administration or spontaneous LH surge. One hundred and forty-five consecutive pregnancies were studied, 99 being viable and 46 nonviable which included subclinical abortion, clinical abortion and ectopic pregnancies. There was a significant difference in the luteal serum progesterone and hCG levels between viable and nonviable pregnancies. There was also a significant difference in the ICON II test result, i.e. either weakly positive (hCG of 25-50 IU/l) and positive (hCG > 50 IU/l) and the pregnancy outcome (p < 0.0001). The specificity of a weakly positive ICON II test in predicting poor pregnancy outcome was 98.8% whereas the sensitivity was 28.6%. In conclusion, a weakly positive ICON II test is useful in predicting poor pregnancy outcome.

Abnormal uterine bleeding

Abnormal vaginal bleeding is a common presenting symptom with an extensive list of potential causes. In evaluating abnormal bleeding, nonuterine causes and pregnancy should first be excluded; after that, it is important to differentiate between ovulatory and anovulatory bleeding (dysfunctional uterine bleeding). Initial laboratory tests, in addition to a sensitive pregnancy test, include hemoglobin and hematocrit determinations, platelet count, and occasionally coagulation studies. An endometrial biopsy or dilation and curettage may be necessary to rule out endometrial hyperplasia or other pathology associated with the long-term unopposed estrogen stimulation experienced by anovulatory patients. In evaluating abnormal ovulatory bleeding, hysteroscopy with selected biopsy or curettage is superior to routine dilation and curettage. Anovulatory patients should be treated with an oral progestin, an oral contraceptive, or, if pregnancy is desired, an ovulation stimulant. Treatment options for patients having ovulatory cycles include an oral contraceptive, an oral progestin, danazol (Danocrine), a gonadotropin-releasing hormone agonist, mefenamic acid (Ponstel), and surgery.

Ectopic Pregnancy

The diagnosis and management of ectopic pregnancy is changing rapidly. More sensitive pregnancy tests and high-resolution transvaginal sonography are making the diagnosis of ectopic pregnancy easier and earlier. In the future, we may become more confident with the ultrasound diagnosis of some ectopic pregnancies such that laparoscopic confirmation will not be required. These patients may be treated with systemic methotrexate. However, at the present time laparoscopy is essential for diagnostic confirmation of most ectopic pregnancies. It is senseless for a skilled laparoscopist to perform a diagnostic laparoscopy, remove the laparoscope, and then proceed with laparotomy or some nonsurgical treatment. There is sufficient evidence in the literature to demonstrate that laparoscopic management of ectopic pregnancies is equally safe, equally effective, and less traumatic than laparotomy. It should replace laparotomy as treatment for most ectopic pregnancies. Unfortunately, there are not enough trained laparoscopists to manage the 88,000 ectopic pregnancies per year in the United States. Operative laparoscopy deserves more emphasis in postgraduate and residency training programs.

Effects of IV Hydration on Levels of hCG in the Serum and Urine of Women With Possible Ectopic Pregnancy

We examined the effects intravenous (IV) hydration on human chorionic gonadotropin (hCG) concentrations in serum and urine during early gestation. Such hydration commonly occurs during the initial evaluation for ectopic pregnancy and has been suggested to cause falsenegative urinary hCG test results. However, previous studies have not included data for specimens taken before and after hydration. Twenty-four patients were studied; 14 had ectopic pregnancies eventually confirmed histologically. All received IV saline (mean volume, 900 mL) over an average of 75 minutes. Serum and urine samples were obtained before and after hydration. Hydration caused a greater decrease (percentage of mean change ± SEM) ofhCG levels in the urine than in the serum, −44% ± 6% vs −13% ± 3%, respectively (P<.05). For serum or urine levels ofhCG, no significant difference in the effects of hydration were found between seven patients with intrauterine pregnancies and the 14 patients with ectopic pregnancies. In no patient did hydration cause a dilution of urinary hCG to below the threshold levels for detection by three rapid bench top immunoabsorption-immunoenzymatic pregnancy tests. A less sensitive pregnancy test, of the agglutination-inhibition type performed on a glass slide, failed to detect six pregnancies initially and eight pregnancies after hydration.

Radiation exposure of fertile women in medical research studies.

Fertile women may be exposed to ionizing radiation as human subjects in medical research studies. If the woman is pregnant, such exposures may result in risk to an embryo/fetus. Fertile women may be screened for pregnancy before exposure to ionizing radiation by interview, general examination, or pregnancy test. Use of the sensitive serum pregnancy test has become common because it offers concrete evidence that the woman is not pregnant (more specifically, that an embryo is not implanted). Evidence suggests that risk to the embryo from radiation exposure before organogenesis is extremely low or nonexistent. Further, demonstrated effects on organogenesis are rare or inconclusive at fetal doses below 50 mSv (5 rem). Therefore, there may be some level of radiation exposure below which risk to the fetus may be considered essentially zero, and a serum pregnancy test is unnecessary. This paper reviews the fetal risks and suggests that consideration be given to establishing a limit to the fetus of 0.5 mSv (50 mrem), below which pregnancy screening need not include the use of a serum pregnancy test.

The evaluation of a pregnancy test (Tandem ICON) in the management of ectopic pregnancy.

A comparison was made between the Tandem ICON and Gravindex tests in the management of suspected ectopic pregnancy in 38 patients. The Tandem ICON test was significantly more accurate than the Gravindex in predicting an ectopic pregnancy. After the exclusion of cases with intrauterine pregnancy, there was no error when the Tandem ICON test was used, but 8 false negative cases were found with the Gravindex.

Time trends of ectopic pregnancies.

Whether the increase of ectopic pregnancies could be explained by methodological problems or by changing age structure was examined in data from one hospital (Tampere, Finland) between 1972 and 1984. Numbers of ectopic pregnancies, births, and induced and spontaneous abortions were obtained by 5-year age-groups and county of residence from the hospital discharge register. Introduction of a more sensitive pregnancy test in 1979 was coincident with the most rapid increase in the role of ectopic pregnancies. Use of incomplete denominators and varying catchment areas and correction of changing age-distribution of pregnant women did not markedly influence the time trends. Our analysis suggests that the observed increase in ectopic pregnancies in this area was partly real and partly due to better diagnosis.

The Use of hCG and Other Pregnancy Proteins in the Diagnosis of Ectopic Pregnancy

Early diagnosis of ectopic pregnancy has been greatly improved by three diagnostic advances: the development of rapid and highly sensitive pregnancy tests, advances in ultrasound examination, and laparoscopy. The estimation of hCG is clinically superior to the measurement of any other pregnancy protein or biochemical parameter. If an hCG test has a sensitivity of 25 IU/1, then 90-100% of ectopic pregnancies will give a positive result. But, the hCG test cannot distinguish between intrauterine and ectopic pregnancy, and here ultrasonic examination and laparoscopy are routine diagnostic measures to identify the site of trophoblastic activity. If highly sensitive hCG tests are used routinely, they may detect small amounts of hCG so early in ectopic pregnancy that the tubal swelling is missed, or hCG may be reminiscent from trophoblastic activity of a previous regressing intrauterine or ectopic pregnancy. The lesson we learn from such cases is that a patient with an elevated hCG level in whom an intrauterine pregnancy has been excluded should be carefully followed-up as long as hCG remains elevated because of the possibility of an early ectopic pregnancy.

Cycle of conception endometrial biopsy

Although controversial, the diagnosis of luteal phase inadequacy and its therapy may improve reproductive outcome, but an endometrial biopsy in the cycle of conception (COC) might theoretically interrupt an intrauterine pregnancy. Fifty-four biopsies obtained in the COC were identified, and patient outcome was documented. Eleven (20%) of the 54 women who underwent COC biopsy did not deliver viable infants. Two patients had ectopic pregnancies, and nine had early abortions, including one whose biopsy specimen contained an early implantation site and another with a trisomy 16 fetus. Although COC endometrial biopsy did not appear to increase the incidence of fetal wastage, biopsy information provided no predictive information suggestive of ultimate pregnancy outcome. Because no useful information is gained from a COC biopsy, we recommend either that pregnancy be avoided or a sensitive pregnancy test be employed for detection in a cycle in which a biopsy is to be performed.

Support for the Woman with an Ectopic Pregnancy

Increased knowledge and awareness among health-care providers as well as technologic advances have decreased the risk of death from ectopic pregnancies. More sensitive pregnancy tests and improved diagnostic procedures have contributed to earlier and more rapid diagnosis of ectopic pregnancy. Also, women in the childbearing years have become more aware of ectopic pregnancy. This has probably contributed to earlier diagnoses and interventions; however, data are not available to substantiate this hypothesis. Research is needed in this area, particularly to study trends in number, causes, and characteristics of women with ectopic pregnancy among reproductive age women (15 to 45 years of age).