CASE REPORT: Severe ovarian hyperstimulation syndrome, selective embryo reduction and heterotopic pregnancy

Ovarian hyperstimulation syndrome is common (21.4%) in patientswith polycystic ovarian disease, treated by gonadotrophins.It is much frequent (50%) in conceptual cycles. We report acase associated with a quadruplet pregnancy that underwent selectiveembryo reduction at 8 weeks' gestation to a twin pregnancy andwas subsequently found to have an unruptured ectopic pregnancyat 11 weeks' gestation. After laparotomy and partial salpingectomya successful twin pregnancy ensued.     

Bleeding following pregnancy loss before 6 weeks' gestation

BACKGROUND: Pregnancy loss before 6 weeks' gestation is common, but little has been reported about the associated bleeding. We compared women's bleeding following a pregnancy loss before 6 weeks' gestation with their typical menstruation. METHODS: Women provided daily urine samples while trying to become pregnant and recorded the number of pads and tampons used each day. Thirty-six women had complete bleed data for a loss before 6 weeks' gestation and one or more non-pregnant cycles. RESULTS: Mean bleed length following a pregnancy loss was 0.4 days longer than the woman's average menstrual bleed (P = 0.01), primarily because of more days of light bleeding. Although there was no overall increase in the total number of pads plus tampons used, women with losses bled less than their typical menses following pregnancies of very short duration and more than usual for the pregnancies lasting the longest. CONCLUSIONS: Overall, the bleeding associated with pregnancy loss before 6 weeks' gestation is similar to menstrual bleeding and unlikely to be recognized as pregnancy loss. The intriguing finding that pregnancies of very short duration were associated with less bleeding than the woman's typical menses might reflect endometrial factors associated with loss.     

Day 14 maternal serum progesterone levels predict pregnancy outcome in IVF/ICSI treatment cycles: a prospective study

BACKGROUND: Serum progesterone has been advocated as a tool in the diagnosis of early pregnancy failure. We conducted this prospective study in order to investigate the potential value of early (14 days after oocyte recovery) serum progesterone measurement, in women undergoing IVF/ICSI and receiving rectal progesterone supplements, in relation to pregnancy outcome. METHODS: 442 women consecutively treated by IVF or ICSI had serum progesterone and bhCG levels prospectively measured 14 days after oocyte retrieval (day 0). All women received natural progesterone 400 mg rectally until the pregnancy test on day 14. Pregnant women were followed up by serial transvaginal ultrasound scans to 8 weeks gestation. RESULTS: 115 women (26%) had a viable intra-uterine pregnancy at 8 weeks gestation, 80 (18.1%) had an abnormal pregnancy (biochemical, ectopic, miscarriage) and 247 (55.9%) failed to conceive. Women with on-going pregnancies had significantly higher serum progesterone levels (median: 430, 95%CI: 390-500 nmol/l) compared to those who had either an abnormal pregnancy (72, 48-96 nmol/l; P < 0.001) or failed to conceive (33, 28-37 nmol/l; P < 0.001). Receiver-operator curve analysis demonstrated that a single serum progesterone on day 14 post-oocyte retrieval, could highly differentiate between normal and abnormal pregnancies (area under the curve = 0.927, 95%CI = 0.89-0.96; P < 0.0001). CONCLUSIONS: In spite of exogenous progesterone supplementation, serum progesterone levels, from as early as 4 weeks gestation (day 14 post-oocyte retrieval) were significantly elevated and predicted women destined to have viable intra-uterine pregnancies. These high levels are suggestive that endogenous progesterone is already sufficient in viable pregnancies and that exogenous progesterone administration will not rescue a pregnancy destined to result in a miscarriage. Single serum progesterone measurement could be a useful indicator of pregnancy outcome in women undergoing IVF or ICSI treatment.     

Pregnancy: Combined intra-uterine and extra-uterine pregnancy in the contralateral tube after gamete intra-Fallopian transfer

A case of combined intra-uterine and contralateral tubal pregnancyafter gamete intra-Fallopian transfer (GIFT) is presented. Laparotomywith partial tubal resection was performed after tubal rupture.The intra-uterine pregnancy is still ongoing without complications.Heterotopic pregnancies are dangerous conditions for the patientand should be taken into account after transfer of multipleoocytes. To our knowledge this is the first report of a heterotopicpregnancy in the contralateral tube after GIFT.     

Embryo reduction in multifetal pregnancies using saline injection: comparison between the transvaginal and the transabdominal approach.

A total of 30 patients with multifetal pregnancies, all resulting from treatment with superovulatory agents or assisted reproductive techniques, underwent embryo reduction. All patients had three or more fetuses (one sextuplet, two quintuplets, seven quadruplets and 20 triplets). The procedure was carried out using intra-embryonal injection of 0.9% sodium chloride solution. Embryo reduction was carried out via the transabdominal approach in 10 patients, performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other patients, at 8-10 weeks of gestation. In the transabdominal group, one patient aborted following repeated attempts at embryo reduction while the other nine gave birth to healthy newborns (eight twins and one triplet). In the transvaginal group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation), 14 pregnancies resulted in a delivery of at least one live newborn (13 twins and one singleton), one patient had a late abortion at 24 weeks' gestation and another was delivered at 27 weeks' gestation due to severe pre-eclampsia. Transvaginal ultrasound-guided needle procedures are commonly practised in most in-vitro fertilization units. The employment of this route for embryo reduction, performed at an earlier gestational age and with the use of a non-toxic substance such as 0.9% saline solution, is advocated.     

Intra-uterine insemination, cervical pregnancy and successful treatment with methotrexate

Cervical pregnancy is rare but one of the most dangerous ofall pregnancy complications. The aetiology of cervical implantationis unclear and because of the fear of profuse haemorrhage abdominalhysterectomy has been historically considered the standard therapy.We report here an unusual case of an infertile woman with cervicalectopic pregnancy after ovulation induction with gonadotrophinsand intra-uterine insemination. The patient was successfullytreated with parenteral methotrexate without significant morbidity.It is concluded that chemotherapy should be initially consideredin most cervical pregnancies either as the sole form of treatmentor to improve the chances of success in alternative conservativemeasures.     

Prenatal sonographic diagnosis of a fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo.

Here we report the first case of prenatally diagnosed fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo. A 37 year old woman, having immunological infertility, was treated by in-vitro fertilization (IVF) and embryo transfer. Following unsuccessful IVF using fresh embryos, the patient conceived after transfer of cryopreserved-thawed embryos. The chromosomal analysis identified a normal karyotype at 16 weeks' gestation when amniocentesis was performed. The pregnancy course was uneventful until 28 weeks' gestation when polyhydramnios associated with fetal renal tumour was detected using ultrasonography. A male infant weighing 2564 g was born via Caesarean section at 34 weeks' gestation. A left nephrectomy was performed 5 days after delivery and the tumour was identified histologically as a mesoblastic nephroma. The postoperative course was uncomplicated to this point.     

Pregnancy: Combined intra-uterine and extra-uterine pregnancy associated with mild hyperstimulation syndrome after clomiphene ovulation induction

We report a combined intra-uterine and tubal pregnancy associatedwith mild ovarian hyperstimulation syndrome (OHSS) followingovulation induction by clomiphene. The diagnosis of ectopicpregnancy was originally missed until rupture occurred. OHSSconfused the clinical pIctures the important diagnostic featurebeing the fail In the haemoglobln concentration. The patienthad a left partial salpingectomy and the uterine pregnancy progressesnormally.     

The value of serum levels of oestradiol, progesterone and beta-human chorionic gonadotrophin in the prediction of early pregnancy loss.

Serial serum levels of oestradiol, progesterone and the beta-subunit of human chorionic gonadotrophin (beta-HCG) had been performed in 674 cycles in women conceiving a singleton pregnancy, either spontaneously or as a result of assisted conception. To determine the value of these estimations in the prediction of early pregnancy loss, frequency distribution curves and receiver operating characteristic curves were derived for the respective hormones measured at weeks 4-7 of gestation and expressed as multiples of the median (MoM) values in pregnancies occurring both with and without ovarian stimulation. A cut-off level of beta-HCG less than 0.5 MoM gave a sensitivity of 68% with an odds ratio of 4.0 at 7 weeks in unstimulated cycles in the prediction of pregnancy failure. A cut-off of 0.8 MoM for progesterone gave a sensitivity of 59% and an odds ratio of 2.8. Prospective hormonal monitoring during the early weeks of gestation may be useful in the prediction of early pregnancy loss and should help to avoid the emergency presentation of some of the complications of early pregnancy, in particular ectopic pregnancy. The limitations imposed by multiple pregnancies and uncertain gestation due to menstrual data may restrict the use of this strategy to specialist fertility centres.     

Pregnancy: Laparoscopy: a dispensable tool in the diagnosis of ectopic pregnancy?

Laparoscopy is regarded as the final decisive diagnostic testin suspected ectopic pregnancy. The new non-invasive diagnosticmethods of transvaginal sonography and serum human chorionicgonadotrophin (HCG) monitoring now challenge this pivotal roleof laparoscopy. In this prospective study the diagnostic valueof an algorithm, combining transvaginal sonography with an HCGcut-off level between 1000 and 1500 IU/I (IRP) was tested in208 consecutive women at risk for ectopic pregnancy. Three diagnosticcategories are designated by the algorithm: intra-uterine pregnancy(n = 73), ectopic pregnancy (n = 89), and trophoblast in regression(n = 46). The latter category represents patients in whom nopregnancy could be located by transvaginal sonography, withan initial HCG concentration < 1500 IU/I, declining duringfollow-up. The algorithm has a sensitivity of 0.97, a specificityof 0.95, a likelihood ratio for a positive test of 19.4, anda likelihood ratio for a negative test of 0.03. The describeddiagnostic strategy thus proved extremely reliable in the safemanagement of patients at risk for ectopic pregnancy, and renderslaparoscopy obsolete.     

236例过期妊娠对母儿影响的分析

目的探讨过期妊娠对母儿的影响.方法对1996年1月至2002年12月在我院分娩的产妇6480作一回顾性分析,将过期妊娠组手术产、孕产期并发症及围产儿病死率高于足月妊娠组.结论应从41孕周起加强产前监护,适时终止妊娠,以降低过期妊娠的发生率,改善母儿预防.     

Improved sensitivity and specificity of a single measurement of serum progesterone over serial quantitative beta-human chorionic gonadotrophin in screening for ectopic pregnancy.

The sensitivity and specificity of a single serum progesterone measurement was compared against two beta-human chorionic gonadotrophin (HCG) measurements 48 h apart in screening for abnormal pregnancy, i.e. ectopic pregnancy, completed or incomplete abortion. Of 1120 patients in the first trimester presenting with a positive urinary pregnancy test, 116/1120 (10.4%) had an ectopic pregnancy, 755/1120 (67.4%) had ultrasonographically confirmed intra-uterine pregnancies, and 249/1120 (22.2%) had abnormal intra-uterine pregnancies documented as complete, incomplete or missed abortions. Of the ectopic pregnancies, 113/116 (97.4%) had a serum progesterone level less than 25 ng/ml while 516/755 (68.3%) viable intra-uterine pregnancies had a serum progesterone level greater than or equal to ng/ml. Of the 1120 patients screened, 402 (35.9%) had both a serum progesterone and two HCG measurements and were eligible for inclusion in this study. Setting a cut-off of 25 ng/ml, the sensitivity and specificity of a single serum progesterone measurement was then compared against two serial HCG measurements, utilizing receiver operating characteristic curves. This analysis demonstrated that a single serum progesterone measurement was significantly more sensitive (P less than 0.05) than two HCG measurements in screening for an abnormal pregnancy. In some patients, a single serum progesterone makes possible the diagnosis of ectopic pregnancy 2 days earlier than two HCG determinations because a second blood sample was not required. We conclude that a single serum progesterone measurement should be added to serial HCG determinations as a standard diagnostic screening test for ectopic pregnancy.     

Successful pregnancy following oocyte donation in a patient with Diamond-Blackfan syndrome and premature ovarian failure

Diamond-Blackfan anaemia (DBA) is a rare congenital conditioncharacterized by profound anaemia associated with an absenceof red cell precursors on bone marrow examination. This reportrepresents the first case of pregnancy following egg donationin a patient with DBA and premature ovarian failure. The patientwas a 24 year old woman who had been diagnosed with DBA whenaged 6 months. Shortly after menarche, the patient became amenorrhoeicand was diagnosed as suffering from premature ovarian failure.She was entered onto an assisted conception programme and conceivedafter one cycle of egg donation. The pregnancy was characterizedby a gradual decline in haemoglobin concentration, reachinga low of 8.1 g/dl, necessitating a single blood transfusionat 29 weeks of gestation. The patient suffered preterm ruptureof the membranes at 29 weeks of gestation and was deliveredby emergency Caesarean section at 30 weeks of gestation becauseof chorioamnionitis and breech presentation. Comparing thiscase with other reports of pregnancy in patients with DBA, ourpatient suffered a less dramatic fall in haemoglobin concentrationand required only a single blood transfusion. It is suggestedthat because the pregnancy arose from donated genetic material,this may have conferred some protective effect.     

Salpingectomy by operative laparoscopy and subsequent reproductive performance

Between January 1984 and August 1991, 511 cases of extrauterinepregnancies were diagnosed by laparoscopy in out department.In 374 cases salpingectomy was performed: 184 by explorativelaparotomy, and 190 by operative laparoscopy. Patients werescheduled for salpingectomy if one or more of the followingcriteria were fulfilled: (i) a ruptured tube which was surgicallyunsuitable for conservation; (ii) no interest in future fertility;(iii) tubes with ectopic gestation previously operated on; (iv)a previous tubal pregnancy on the same side, which was treatedexpectantly. Salpingectomy was performed via operative laparoscopywith bipolar diathermy forceps and laparoscopic scissors. Pregnancyrates, i.e. intra-uterine and repeat extra-uterine, were evaluated.The reproductive performance following salpingectomy did notdiffer significantly, whether by laparotomy or laparoscopy:the intra-uterine pregnancy rate was 78 and 64%, respectivelyand the repeat ectopic pregnancy rate was 12 and 6%, respectively.Salpingectomy via laparoscopy can be performed safely with alow incidence of complications, with subsequent reproductiveperformance comparable to laparotomy.     

Pregnancy: The expectant management of early pregnancies of uncertain site

The role of expectant management was evaluated in 80 women inwhom clinical examination, including vaginal ultrasound, hadfailed to identify the location of an early pregnancy. In 45cases, spontaneous resolution of the pregnancy products occurred.A normal intra-uterine pregnancy was diagnosed in 12 patients.A total of 23 patients underwent active therapeutic measuresdue to an ectopic pregnancy (n = 16) or a spontaneous abortion(n = 7). The effectiveness of different diagnostic measuresto identify patients suitable for expectant management was analysed.In 33/34 patients (97%) with a relative daily human chorionicgonadotrophin (HCG) change of <–5%, and a serum progesteroneconcentration of <20 nmol/l, spontaneous resolution of thepregnancy products occurred. Among 46 cases, with a relativedaily HCG change of >–5% and/or serum progesterone>20 nmol/l, active therapeutic measures were carried outin 22 cases (48%), a normal intra-uterine pregnancy was diagnosedin 12 cases (26%) and spontaneous resolution of the pregnancyproducts occurred in 12 cases (26%). In conclusion, the combinationof a single progesterone assay and serial HCG determinationsretrospectively identified early pregnancies of uncertain locationin whom expectant management was a safe management option.     

Effect of first-trimester serum from pregnant women with high-resistance uterine artery Doppler resistance on extravillous trophoblast invasion

BACKGROUND: Abnormal uterine artery Doppler indices are associated with pregnancy complications such as pre-eclampsia and intrauterine growth restriction. Poor trophoblast invasion may be a consequence of, or be associated with, abnormal Doppler indices. OBJECTIVE: To evaluate in vitro trophoblast function following exposure to first-trimester serum from pregnancies with high uterine artery Doppler resistance indices. METHODS: Doppler ultrasound examination of the maternal uterine arteries was performed on women at 10-14 weeks' gestation. Serum was collected from women with bilateral uterine artery notches with resistance indices above the 95th centile and from patients with normal uterine artery indices. The effect of serum on trophoblast invasion was determined using an established in vitro model from the extravillous trophoblast-derived cell line SGHPL-4. RESULTS: Trophoblastic invasion was significantly reduced when treated with serum from women with high-resistance compared with normal-resistance uterine artery Doppler indices (P < 0.05). CONCLUSION: Maternal serum in the first trimester of pregnancy from patients with high-resistance uterine artery Doppler indices appears to inhibit trophoblast invasion. This experimental model allows further investigation of factors responsible and the evaluation of therapeutic strategies.     

Local medical treatment of interstitial pregnancy after in-vitro fertilization and embryo transfer (IVF--ET): two case reports

Two cases of interstitial pregnancy (one singleton, one heterotopictwins) were confirmed 31 and 34 days after in-vitro fertilization.Serum human chorionic gonadotrophin concentrations were 35 000and 86 000 mlU/ml, respectively. They were treated conservativelywith transvaginal ultra-sonically guided intra-ovular injectionof either methotrexate in the singleton pregnancy, or potassiumchloride into the ectopic sac of the heterotopic twins. No complicationswere observed. The intra-uterine pregnancy continued and thepatient delivered a 3350 g healthy baby at 39 weeks.     

Use of reticulin stain in the diagnosis of intra-uterine gestation

AIMS: The diagnosis of intra-uterine gestation may be problematic when specimens from clinically suspected products of conception lack chorionic villi and/or fetal somatic tissues, since the distinction of intermediate trophoblast from decidual or myometrial elements can be difficult. The placental site is also characterised by stromal changes, including the deposition of a characteristic extracellular fibrinoid matrix. We have noted that these stromal changes may be highlighted by a simple reticulin stain; therefore, we have evaluated reticulin staining in a series of endometrial biopsy specimens from patients with intra-uterine and ectopic gestations. METHODS: Reticulin staining was performed in 28 endometrial specimens from patients with first trimester intra-uterine gestations, including 14 cases that lacked chorionic elements. Eight endometrial samples from patients with concurrent histologically verified tubal ectopic pregnancy were also examined. Selected cases were also studied using a Masson trichrome stain, and immunohistochemically with antisera to cytokeratin and HPL. RESULTS: There was a distinct increase in reticulin staining, usually evident at low power magnification, in most areas of decidua showing implantation site. Prominent reticulin staining was present around the decidual and trophoblast cells and there was also accentuation around stromal vessels, glands and myometrial cells. There was no clear difference in staining within areas of decidua including only rare intermediate trophoblast cells but this pattern was seldom seen in isolation. Minimal changes were seen in the placental site using the Masson trichrome stain. CONCLUSION: Reticulin stains may prove useful in the assessment of endometrial specimens from patients with purported intra-uterine gestations when chorionic elements are not identified. Since the staining technique is simple and can be quickly performed, it could be used as an adjunct to conventional H&E assessment and to select appropriate specimen blocks for additional more sensitive studies, including immunohistochemistry.     

Heterotopic pregnancies after in-vitro fertilization and embryo transfer--a Danish survey

Thirteen cases of heterotopic pregnancy were diagnosed among1171 pregnancies established in Denmark after in-vitro fertilizationand embryo transfer (IVF-ET). Thus the frequency of heterotopicpregnancy was 13/1171 or 1.1%. In five cases the diagnosis ofheterotopic pregnancy was made by ultrasound at 6–9 weeksof gestation; three of these patients were asymptomatic, whiletwo patients presented with abdominal pain and vaginal bleeding.All these patients had an unruptured ectopic pregnancy. Eightcases were diagnosed at the time of surgery; all these patientspresented with abdominal pain. Only two of the 13 patients hadvaginal bleeding. In nine of the 13 cases the intra-uterinepregnancy resulted in term delivery, while one pregnancy isongoing. In pregnancies following IVF-ET, this diagnosis shouldparticularly be considered in cases with abdominal pain; vaginalbleeding may be absent. Ultrasound examination may lead to earlydiagnosis even in asymptomatic cases. In most cases, removalof the ectopic gestation will allow the intrauterine pregnancyto proceed to term.     

Pregnancy: Heterotopic pregnancy obtained after in-vitro fertilization and embryo transfer following bilateral total salpingectomy: case report

Heterotopic (coexistent ectopic and intra-uterine) pregnancyis common following in-vitro fertilization and multiple embryotransfer. Total bilateral salpingectomy is generally consideredto eliminate the risk of ectopic, and hence heterotopic pregnancy.This is, however, not strictly correct as it does not eliminatethe risk of interstitial tubal pregnancy. This is the firstreported case of a heterotopic pregnancy following total bilateralsalpingectomy. The diagnostic pitfalls and a suggested methodof avoiding them are discussed.