Serum progesterone and 17-hydroxyprogesterone in the diagnosis of ectopic pregnancies and the value of progesterone replacement in intrauterine pregnancies when serum progesterone levels are low.

The corpus luteum function was evaluated in patients with surgically confirmed ectopic pregnancy (EP) in a multicenter study. In addition, the minimal threshold of serum progesterone (P) concentration required for salvaging intrauterine pregnancies (IUP) was also examined. Results show that single P or 17-OHP measurements are not diagnostic for EP, since mean P levels in EP were similar to those with spontaneous abortion though significantly lower than those in controls. 17-OHP levels in EP overlapped in 50% with IUP, and the mean levels were significantly lower only at 6-7 weeks. The 17-OHP levels when compared to hCG supports the view that corpus luteum defect is primary. In IUP, P levels < 8 ng/ml still were associated with viable (60%) pregnancy; thus no minimal threshold could be established.     

Retrospective analysis of laparoscopic salpingostomy and conservative expectant management of tubal ectopic pregnancy

Purpose  To identify predictive factors for successful expectant management of ectopic pregnancy and to evaluate the prognosis for fertility after expectant management and laparoscopic salpingostomy. Methods  Forty-six cases of expectant management and eighty cases of laparoscopic salpingostomy for tubal ectopic pregnancy were retrospectively analyzed. Subjects were classified in three groups: those who underwent laparoscopic salpingostomy, those treated by expectant management only, and those treated by expectant management but requiring additional treatment. Results  The rates of tubal patency, intrauterine pregnancy and repeated ectopic pregnancy in the laparoscopic salpingostomy group were 75, 40, and 16%. The rates in the expectant management group were not significantly different: 72, 42 and 15%. Finally, the rates in the extra treatment group were 75, 39 and 15%. Success rate of expectant management was 54%. In 93% of cases expectant management was successfully completed when the initial levels of urinal hCG were less than 3000 mIU/ml and the levels of hCG 48 h later were less than 80% of the initial levels. However, expectant management alone was insufficient and required extra treatment in 90% of cases when the initial levels of hCG were 3000 mIU/ml and above or when the levels of hCG level 48 h later was 80% of initial levels and above. Conclusions  Expectant management in combination with salpingostomy is not only minimally invasive but also a useful way to preserve fertility. Initial urine hCG levels and their variation over time can help predict whether expectant management will succeed.     

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.     

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.     

CA-125 levels in ruptured and unruptured tubal ectopic pregnancies

AIM: This prospective, single-blind and controlled clinical study aimed to research if CA-125 levels could be a useful test in the differential diagnosis of intact and ruptured tubal ectopic pregnancy. METHODS: Sixty-five women with tubal ectopic pregnancy of 5-10 weeks' duration (27 women with ruptured tubal ectopic pregnancy [REP] and 38 women with unruptured tubal ectopic pregnancy [UREP]) and 65 women with normal intrauterine pregnancy (NIUP) of the same gestational age were studied prospectively. Serum CA-125 levels were measured in all women and these levels were compared among the REP, UREP, and NIUP groups. RESULTS: The mean CA-125 levels didn't show any significant difference between the REP and NIUP groups (P > 0.05). The mean CA-125 levels of these two groups were higher than that in the UREP group (P < 0.01, P < 0.001, respectively). The dispersion ratios of the CA-125 levels had a statistically significant difference between the REP and UREP groups (chi(2): 42.44, P < 0.0001). CA-125 levels weren't correlated with gestational weeks in the REP and UREP groups (r: 0.005, P > 0.05; r: 0.008, P > 0.05, respectively). CONCLUSION: In intact tubal ectopic pregnancies, expectant or managed with medical treatment, the increase of CA-125 levels in the serial measurements could be a supplementary test for an early diagnosis of tubal rupture.     

雌孕激素水平与胚胎移植助孕后异位妊娠相关性探讨

目的 探讨超生理雌孕激素水平在胚胎移植助孕后异位妊娠发生中的意义.方法 对1997年9月至2006年10月在河北医科大学第二医院生殖医学科行新鲜胚胎和冻融胚胎移植获得妊娠407周期进行回顾性分析.结果 新鲜胚胎和冻融胚胎移植周期异位妊娠率分别为7.45%、1.18%,差异有统计学意义(X2=4.5958,P=0.0321).新鲜周期中异位妊娠组与非异位妊娠组输卵管因素比例分别为79.2%、56.4%.异位妊娠组胚胎移植后3d血清孕酮[(120.1±32.3)nmoL/L]明显高于非异位妊娠组[(89.7±43.7)nmol/L],差异均有统计学意义(P<0.05).结论 超生理雌孕激素水平及其比例失调可能与胚胎移植助孕后异位妊娠发生有关,并在异位妊娠的发生中与输卵管受损联合起作用.     

The management of ectopic pregnancies and pregnancies of unknown location

Since the introduction of dedicated Early Pregnancy Units and the use of high-resolution transvaginal probes ectopic pregnancies are diagnosed at earlier gestations. As a result, the treatment options in the management of ectopic pregnancies have diversified. In this review, the role of transvaginal sonography in the management of women with ectopic pregnancies is described and the different treatment modalities available in their management are critically evaluated. We assert that ectopic pregnancy should be diagnosed on the basis of positively visualising an adnexal mass using transvaginal sonography, rather than the absence of an intrauterine pregnancy. If a pregnancy cannot be seen, either inside or outside the uterus, this should be described as a pregnancy of unknown location and managed expectantly until the outcome is confirmed.     

A preoperative classification to predict the intrauterine and ectopic pregnancy rates after distal tubal microsurgery

A simple preoperative classification is described to predict the intrauterine and ectopic pregnancy rates following distal tubal microsurgery. Laser CO2 microsurgical salpingostomies were performed on 76 patients between January 1979 and January 1984. All of the patients underwent a preoperative assessment, which included hysterosalpingogram and laparoscopy, to formulate a preoperative classification based on a point system. The patients were divided into four groups according to tubal damage, with a subsequent intrauterine pregnancy rate of 58.3% in grade I, 36.6% in grade II, 9.5% in grade III, and 0% in grade IV. The patients were divided into four groups according to adhesions, with a subsequent intrauterine pregnancy rate of 38.8% with no adhesion, 32.0% with mild adhesions, 26.6% with moderate adhesions, and 5.5% with severe adhesions. From these results, a preoperative management is proposed for patients being considered for either distal tubal microsurgery or in vitro fertilization.     

Human chorionic gonadotrophin and progesterone levels in pregnancies of unknown location.

OBJECTIVE: To evaluate accuracy, user variability and impact of experience on the use of serum hCG and progesterone in women who have a pregnancy of unknown location (PUL's). MATERIALS AND METHODS: This was a retrospective study. Presenting 1932 consecutive women to an Early Pregnancy Unit had a transvaginal scan. The location of the pregnancy could not be found in 189 women (Pregnancy of unknown location, PUL), and so blood was taken to measure serum hCG and progesterone at presentation and subsequently after 48 h, according to the protocol. All women were monitored at regular intervals until the final outcome was known, which was a failing PUL, a viable or failing intra-uterine pregnancy, an ectopic pregnancy or a persisting PUL. The final study group comprised 185 PUL, as four cases of persisting PUL were treated and excluded from the analysis. Five investigators assessed the hormonal data independently. The investigator's experience as defined by the number of years working in obstetrics and gynecology ranged from 2 to 15 years. Each investigator knew the women were clinically stable and that the scan result was consistent with a PUL, i.e. there were no signs of intra- or extra-uterine pregnancy, and there was no hemoperitoneum on TVS. When assessing the PUL's, each investigator was given the hormonal results at time 0 and 48 h for serum hCG and progesterone and asked to classify the PUL's as failing PUL's, immediately viable intra-uterine PUL's and ectopic PUL's. No other clinical information about the women was made available. RESULTS: Complete data 185 women (89%): 102 failing PUL's, 63 immediately viable intra-uterine PUL's and 20 ectopic PUL's (total 185). The most experienced investigator obtained the best accuracy 163/185 (88.1%); not significantly different from those obtained by less experienced investigators (range 85.9-87.6%). Mean correct classification of failing PUL and immediately viable intra-uterine PUL's was 93% (range 89-95%); corresponding value for ectopic PUL's was 42% (range 25-60%). Agreement between observers for classification of failing PUL's and immediately viable intra-uterine PUL's was almost perfect (Cohen's kappa 0.86-0.90), whereas the value for ectopic PUL's group was fair to moderate (Cohen's kappa 0.39-0.67). All 5 investigators misdiagnosed same 35% of ectopic PUL's. CONCLUSIONS: Serum hCG and progesterone levels at defined times can be used to predict the immediate viability of a PUL, but cannot be used reliably to predict its location. Clinical experience does not significantly improve the ability to assess PUL outcome.     

Serum CA-125 levels in women with ectopic and intrauterine pregnancies.

In women with ectopic pregnancies the extrauterine compartments are exposed to fetal tissue. Since such tissue is known to express CA-125, we measured serum levels of CA-125 in patients with ectopic pregnancies and compared them to those in patients with intrauterine pregnancies. A total of 44 pregnant women were included in the study; all were in the first trimester. Twenty-seven of them had ectopic pregnancies, and 17 had intrauterine ones. Our results show that women with ectopic pregnancies, ruptured or unruptured, were more likely to have elevated levels of serum CA-125 than were women who had intrauterine pregnancies.     

Low serum progesterone levels and tubal dysfunction--a possible cause of ectopic pregnancy

We analyzed 22 human oviducts by the suction electrode method for electrical activity (preceding and reflecting the mechanical activity), as related to serum progesterone levels. Eleven patients had high progesterone levels (greater than or equal to 20 nmol/L), but the other 11 patients had low levels. When the serum progesterone level was low, the oviductal electrophysiologic characteristics were those associated with poor ovum transfer: low probability of prouterine propagation of the activity at the fimbrial end of the tube: high-frequency but low number of electrical bursts, reflecting possible weak propulsive force; and a high occurrence rate of sine-wave-like activity and inactive areas where ovum retention can occur. These phenomena could be related to the higher incidence of ectopic pregnancies in patients with luteal phase defect.     

Serum progesterone levels as an aid in the diagnosis of ectopic pregnancy

Progesterone levels in 29 women with ectopic pregnancies and 20 women with early intrauterine pregnancies were evaluated using a new direct radioimmunoassay that offers results within four hours. Patients with normal intrauterine pregnancies had serum progesterone levels greater than 20 ng/mL (mean = 30.9 ng/mL) while all patients with ectopic pregnancies had progesterone levels less than 15 ng/mL (mean = 5.7 ng/mL). The incorporation of the progesterone assay into the workup of a patient with suspected ectopic pregnancy can be a useful clinical adjunct to the conventional methods of evaluation.     

Beta human chorionic gonadotropin levels in cul-de-sac blood of patients with ectopic pregnancies

hCG levels in cul-de-sac and peripheral blood in patients with ectopic pregnancies were studied. hCG levels were significantly higher in the cul-de-sac blood than in peripheral blood (P less than 0.01). The high hCG level in the cul-de-sac blood was not due to interference by proteolytic enzymes in cul-de-sac blood since the protease inhibitors, aprotinin and phenylmethylsulfony fluoride, did not alter the RIA results from cul-de-sac samples, nor did Con-A chromatography of the samples. Assay of cul-de-sac blood samples for hCG may increase the sensitivity of diagnosing ectopic pregnancies.     

A new technique in the laparoscopic resection of cornual ectopic pregnancies: a case series

Cornual ectopic pregnancies are a challenging dilemma faced in the early pregnancy setting. They are associated with high morbidity and mortality rates when compared to standard tubal ectopic pregnancies mainly due to their late presentation and significant haemorrhage and hysterectomy risk. Laparoscopic resection has been described successfully; however, the procedure can be technically very challenging and can carry significant potential risks of bleeding and conversion to laparotomy. Carboprost is a synthetic prostaglandin analogue, used widely in the management of obstetric haemorrhage, with its main mode of action being myometrial contractions. We present a series of four cases where intramyometrial carboprost injection was used successfully, prior to the laparoscopic resection of cornual ectopic pregnancies, to produce consistent and reproducible surgical benefits including prolonged myometrial contractions and subsequent reduced uterine blood flow. This results in a significant reduction in intraoperative blood loss as well as a clearer demarcation of the ectopic pregnancy and a technically easier resection.     

Comparison of maternal serum estradiol and progesterone levels in pregnancies after induced and spontaneous ovulation

Summary Maternal serum estradiol and progesterone levels during the early 6th to 15th weeks of gestation, were measured by radioimmunoassay in 140 pregnancies following induction of ovulation with gonadotropins or clomiphene citrate. The levels were compared with those observed in 79 spontaneous pregnancies. Significantly higher levels were observed in gonadotropin and clomiphene citrate induced pregnancies (bothP values <0.001) between the 6th to 9th week of gestation as compared to spontaneous pregnancies. Steroid levels were similar in the two groups from the 9th week onwards. No statistically significant differences in steroid hormone values were observed in aborted and successful pregnancies within each group studied. We conclude that ovulation induction is associated with higher estradiol and progesterone levels until placental steroidogenesis starts.