High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies

Antiphospholipid antibodies (APA), lupus anticoagulant (LA)and/or anticardiolipin antibodies (ACA), are associated withthrombosis and recurrent miscarriage. We studied the outcomeof 20 pregnancies in women (median age 32 years; range 23–41)with APA (14 LA positive; three immunoglobulin (Ig) G ACA positive;two IgM ACA positive and one LA and IgG ACA positive) and historyof recurrent miscarriage (median 4; range 3–11) who declinedpharmacological treatment in their next pregnancy. Comparisonwas made with a cohort of 100 consecutive women (median age33 years; range 23–44) with recurrent miscarriage (median4; range 3–10), in whom no underlying cause to accountfor their pregnancy losses was found. Of the 20 women with APA,18 (90%) miscarried compared to 34 of the 100 women (34%) withnormal investigations (P < 0.001). The majority (94%) ofmiscarriages in women with APA occurred in the first trimester.Fetal heart activity was seen prior to fetal death in 86% ofwomen with APA compared to 43% of women with normal investigations(P < 0.01). The first trimester loss of embryonic pregnanciesis the most common type of miscarriage in women with APA. Thismay be a result of defective implantation and subsequent placentation.     

Pregnancy: The influence of the number of embryos transferred in 1060 in-vitro fertilization pregnancies on miscarriage rates and pregnancy outcome

To assess the incidence of miscarriage, multiple pregnancy andoutcome of pregnancy in relation to the number of embryos transferredduring in-vitro fertilization (IVF), an analysis was performedof 1060 pregnancies conceived in a tertiary-referral IVF clinic.There was no difference in the miscarriage rate after transferof one or two embryos (37.7% and 34.6%), or after three or fourembryos (22.5% and 25.2%). The miscarriage rate was, however,higher when one or two embryos were transferred compared withthree (P < 0.01) or four embryos (P < 0.02). Of the 724ongoing pregnancies, 524 (72.3%) were singleton, 164 (22.7%)twin, 33 (4.6%) triplet and three (0.4%) quadruplet. The mean(±SD) ages of women with singleton, twin, triplet andquadruplet pregnancies were 32.5 (±3.8), 32.0 (±3.5),29.76 (±4.3) and 29.67 (±2.5) years respectively.The mean age of women with singleton and twin pregnancies wassimilar and both were greater than that of triplet pregnancies(P < 0.007). The overall perinatal mortality rate (PNMR)was 39.7/1000. The PNMR for singletons was 17.2/1000, for twins80.0/1000 and for triplets 30.6/1000. All of the babies fromthe three quadruplet pregnancies survived. There were more babieslost in the twin pregnancies than any other group, althoughthis only reached significance for singletons versus twins (P< 0.00005). We conclude that the incidence of miscarriageis increased in women in whom one or two embryos are transferred.Multiple pregnancies are more likely to occur in younger womenand are associated with a significantly higher rate of perinatalmortality.     

Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage

Activated protein C (APC) resistance, both in its congenital form, due to the factor V Leiden mutation, and in its acquired form, are important risk factors for systemic venous thrombosis. In view of the suspected thrombotic aetiology of some cases of recurrent miscarriage, the prevalence of APC resistance was determined among 1111 consecutive Caucasian women with a history of either recurrent early miscarriage (three or more consecutive pregnancy losses at <12 weeks gestation; n = 904) or a history of at least one late miscarriage (>12 weeks gestation; n = 207). A control group of 150 parous Caucasian women with no previous history of adverse pregnancy outcome was also studied. Acquired APC resistance was significantly more common among both women with recurrent early miscarriage (8.8%: 80/904; P = 0.02) and those with late miscarriage (8.7%: 18/207; P = 0.04) compared with controls (3.3%: 5/150). In contrast, the frequency of the factor V Leiden allele was similar among (i) women with recurrent early miscarriage (3.3%:60/1808; 58 heterozygotes and one homozygote), (ii) those with late miscarriage (3.9%:16/414; 14 heterozygotes and one homozygote) and (iii) the control group (4.0%:12/300; 12 heterozygotes). Acquired but not congenital APC resistance (due to the factor V Leiden mutation) is associated with both early and late miscarriage.     

Immunology: Prognostic significance of maternal DR histocompatibility types in Danish women with recurrent miscarriages

In a previous case-control study of women with unexplained recurrentmiscarriages we reported that the frequency of women positivefor each of the two histocompatibility (HLA) types HLA-DR1,Br and HLA-DR3 was increased in a subset of patients with ahistory of four or more miscarriages. In the present study weexamined whether the increased frequency of the two HLA typesin this subset of patients indicated that they would resultin a poor pregnancy prognosis. We related pregnancy outcomesto the mothers' HLA-DR type in a prospective study of a well-defined,closely supervised group of 94 women with unexplained recurrentmiscarriages who had achieved intra-uterine pregnancy in thecourse of one of two prospective placebo-controlled trials concerningthe efficacy of immunotherapy. Of the patients who were HLA-DR1,Br and/or HLA-DR3 positive 62% miscarried their next pregnancycompared with 29% of the patients negative for the two HLA types[relative risk of miscarriage in the former group = 2.2 (P <0.002)unadjusted, and 1.8 (P = 0.025) when adjusted for the numberof previous miscarriages]. The results suggest that Danish womenwith unexplained recurrent miscarriages who are positive forHLA-DR1, Br and/or -DR3 display a poorer pregnancy outcome thanpatients negative for these types.     

Factor V Leiden and recurrent miscarriage-prospective outcome of untreated pregnancies

BACKGROUND: Some cases of recurrent miscarriage and later pregnancy complications have a thrombotic basis. Factor V Leiden is a common thrombophilic mutation. METHODS: The prospective outcome of untreated pregnancies amongst 25 women heterozygous for the Factor V Leiden allele who had a history of either recurrent early miscarriages only (three or more miscarriages at <12 weeks gestation; n = 19) or of late miscarriage (>12 weeks gestation; n = 9) was studied. Control groups of women with a similar pregnancy history but who had a normal Factor V genotype were also studied. RESULTS: The live birth rate was significantly lower amongst women with a history of recurrent early miscarriage who carried the Factor V Leiden allele (6/16; 37.5%) compared with that amongst those with a normal Factor V genotype (106/153; 69.3%; odds ratio 3.75, 95% confidence intervals 1.3-10.9). The live birth rate was 11.1% (1/9) amongst those with a history of late miscarriage carrying the Factor V Leiden allele and 48.9% (22/45) amongst those with a normal Factor V genotype. CONCLUSIONS: Attention should be directed at screening women with recurrent miscarriage associated with placental thrombosis for Factor V Leiden and a policy of targeted thromboprophylaxis during future pregnancies should be assessed in the form of a randomized controlled trial.     

Endocrinology: Luteal phase oestradiol and progesterone levels are stronger predictors than follicular phase follicle stimulating hormone for the outcome of in-vitro fertilization treatment in women with tubal infertility

Basal follicle stimulating hormone (FSH) in a natural cycle,FSH on cycle days 3 and 10 in a domiphene citrate-stimulatedcycle and oestradiol and progesterone area under the curve (AUC)in the luteal phase of the ciomiphene citrate-stimulated cyclewere evaluated as hormonal predictors for the outcome of FVFtreatment in 53 normally cycling women with tubal infertility.The pregnant women had significantly fewer treatment cycles(P < 0.001) and needed fewer ampoules of gonadotrophins (P< 0.001). They also had more oocyte retrievals (P < 0.001),more oocytes per retrieval (P < 0.01), higher fertilizationrate (P < 0.001) and more replaced pre-embryos per replacement(P < 0.01) as compared with non-pregnant women. Significantdifferences were found in FSH concentrations on cycle days 3(P < 0.05) and 10 (P < 0.001) after domiphene citratestimulation and for oestradiol and progesterone AUC in the lutealphase (P < 0.001) between those women who became pregnantand those who did not become pregnant after IVF treatment Lutealoestradiol and progesterone had considerably stronger predictivevalue for the outcome of IVF treatment as compared to basalFSH and domiphene citrate challenge test.     

Recurrent miscarriage--an aspirin a day?

Recurrent miscarriage and later pregnancy complications are in some cases associated with placental thrombosis and infarction. The aim of this study was to assess the value of low dose aspirin (75 mg daily) in improving the subsequent livebirth rate amongst women with either unexplained recurrent early miscarriage (<13 weeks gestation; n = 805) or unexplained late pregnancy loss (n = 250). Amongst women with recurrent early miscarriages, there was no significant difference in the livebirth rate between those who took aspirin (251/367; 68.4%) compared with those who did not take aspirin [278/438; 63.5%; odds ratio (OR) 1.24; 95% confidence interval (CI) 0.93-1.67]. This relationship was independent of the number of previous early miscarriages. In contrast, women with a previous late miscarriage who took aspirin had a significantly higher livebirth rate (122/189; 64.6%) compared with those who did not take aspirin (30/61; 49.2%: OR 1.88; 95% CI 1.04-3.37). The empirical use of low dose aspirin amongst women with unexplained recurrent early miscarriage is not justified. We are currently investigating the role of incremental doses of aspirin in the treatment of women both with early miscarriages associated with thrombophilic abnormalities and in those with late pregnancy losses.     

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.      

Pregnancy: Determinants of reproductive prognosis after ectopic pregnancy

The reproductive prognosis of 115 women desiring pregnancy whounderwent surgery for ectopic pregnancy between 1985 and 1990at the Clinica Luigi Mangiagalli, was analysed after a medianfollow-up period of 26 months (range 2–83). Probabilityof reproductive events was assessed by a product-limit model.Women who underwent surgery for ectopic pregnancy had a 54%probability of becoming pregnant (cumulative pregnancy rate,CPR) and a 36% probability of giving birth to a child (cumulativelivebirth rate, CLB) during the 3 years after surgery. Thesepercentages dropped with history of previous ectopic pregnancy(respectively 33%, P = 0.07, and 7%, P < 0.05). Increasingage at surgery and presence of adhesions in the contra-lateraltube seemed to be associated with poor reproductive prognosis(CPR = 40% and CLB = 12% for women aged 35 years and CPR = 37%and CLB = 20% in women with adhesions in the contra-lateraltube), but these findings were not statistically significant.No association emerged between fertility and parity or typeof surgery. The recurrence rate of ectopic pregnancy was 20%.No significant association emerged between recurrence of ectopicpregnancy and age, history of previous pregnancy, history ofprevious ectopic pregnancy, non-intact contra-lateral tube andsalpingotomy.     

High and low BMI increase the risk of miscarriage after IVF/ICSI and FET

BACKGROUND: The extremes of BMI are associated with an increased risk ofmiscarriage both in spontaneously conceived pregnancies andafter fertility treatment. The aim of the present study wasto study the effect of BMI on miscarriage rate (MR) in freshIVF/ICSI, and in spontaneous and hormonally substituted frozen-thawedembryo (FET) cycles. METHODS: Analysis was carried out on 3330 first pregnancy cycles, performedduring the years 1999–2004, of which 2198 were fresh,666 were spontaneous and 466 were hormonally substituted FETcycles. A categorical, a linear and a quadratic models of theeffect of BMI on miscarriage were studied by logistic regression.Factors related to patient characteristics, protocol and embryoparameters were also examined. RESULTS: MR was higher in hormonally substituted FET (23.0%), comparedwith the fresh cycles (13.8%) and spontaneous FET (11.4%, P< 0.0001). Multivariate logistic regression revealed thatthe relationship between BMI and the risk of miscarriage isnot linear but quadratic (U-shaped) (P = 0.01), indicating ahigher risk of miscarriage in underweight and obese women. Hormonalsubstitution for FET was also associated with a 1.7-fold higherMR, compared with the fresh cycles (P = 0.002, 95% confidenceinterval 1.2–2.3). CONCLUSIONS: Obese and underweight women have an increased risk of miscarriage,and hormonally substituted FET is associated with an even higherMR.     

Pregnancy: An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases

A total of 500 consecutive women (mean age 32.9 years; SD 5years) presenting with a history of recurrent miscarriages (median4; range 3–17) were investigated for the presence of antiphospholipidantibodies (APA), polycystic ovaries (PCO), hypersecretion ofluteinizing hormone (LH) and chromosome abnormalities in orderto detect an underlying cause of their pregnancy losses. Allwomen had details of their previous reproductive history, investigationsand treatment documented: 76% of the women had experienced onlyearly pregnancy losses (miscarriage <13 weeks gestation);32% had a history of subfertility; and significant parentalchromosome rearrangements were present in 3.6% of couples. Anultrasound diagnosis of PCO was made in 56% of women, 58% ofwhom were demonstrated to hypersecrete LH, based on early morningurinary LH analysis. Circulating APA were found in 14% of women.An underlying cause of recurrent miscarriage—genetic,endocrine or autoimmune—was found in >50% of couples.Women in the latter two groups are being recruited to randomizedtreatment trials which are discussed.     

Pregnancy: Serum concentrations of luteinizing hormone and progesterone in ovum recipients: their relationship with pregnancy and miscarriage

Our objective was to test the hypothesis that the associationbetween elevated luteinizing hormone (LH) concentrations andmiscarriage is mediated via an effect of LH on the maternalenvironment, rather than on the oocyte. The impact of maternalage, ovarian function, previous IVF attempts, therapeutic (buserelin)and hormonal (LH, oestradiol, progesterone) effects occurringon the day of zygote intra-Fallopian transfer (ZIFT) or embryotransfer, and of oocyte or embryo numbers, whether they werefresh or frozen, and their mode of transfer on the occurrenceof pregnancy and miscarriage following ovum donation (n = 57)were investigated. The cycles were divided by outcome into non-pregnant(n = 26), miscarriage (n = 19) and normal term pregnancy (n= 12). The circulating concentrations of LH were greater inmiscarriage cycles (P = 0.046) and cycles ending in pregnancy(P = 0.04) than in non-pregnant cycles, while the concentrationsof progesterone were greater in non-pregnant (P = 0.029) andmiscarriage (P = 0.015) cycles than in cycles ending in pregnancy.Frozen embryos were used more frequently in non-pregnant comparedto cycles ending in pregnancy (P = 0.016). Multiple regressionanalysis was used to investigate which factors are associatedwith miscarriage and identified progesterone concentrationsat the time of transfer as being the only significant variable(r = 0.48, F = 8.5, P = 0.007). The same method of analysiswas used to investigate which factors are associated with thefailure to conceive and identified previous IVF attempts (F= 5.8, P = 0.021), the presence of ovarian function (F = 5.7,P = 0.022), the use of frozen zygotes (F = 5.1, P = 0.029) andprogesterone concentrations (F = 5.9, P = 0.02), with an overallresult of r = 0.59, F = 5.2 and P = 0.002. In conclusion, highprogesterone concentrations were associated with the failureto conceive and miscarriage. In contrast, LH concentrationswere lower in women who failed to conceive but similar in pregnantwomen who did and did not miscarry. This suggests that the associationbetween elevated LH concentrations and infertility is via adirect effect of LH on the oocyte and an indirect effect, mediatedby elevated progesterone concentrations, on the endometrium.     

Autoantibodies and antisperm antibodies in sera and follicular fluids of infertile patients; relation to reproductive outcome after in-vitro fertilization

Immune reactions have effects at various concentrations in thereproductive process and autoantibodies may have an impact onfertility and the outcome of assisted conception. We measuredthe prevalence of and relation between antibodies to smoothmuscle, nuclear, phospholipid and sperm antigens, and concentrationsof immunoglobulins G, M and A and complement components C3 andC4, in the sera and follicular fluids of women with unexplainedinfertility (n = 30), endometriosis (n = 20), tubal infertility(n = 50) and the sera of 20 normal non-pregnant women. We assessedfertilization and successful pregnancy rates in relation toantibody status of infertile women after in vitro fertilization.All antibodies had a higher prevalence in infertile women comparedwith controls and this was significant for smooth muscle antibodyin endometriosis (P < 0.05); anticardiolipin antibody intubal infertility P < 0.05); and antisperm antibody in alltypes of infertility (P < 0.001). There was no relation betweenpresence of specific antibodies in serum or between serum andfollicular fluids. Total biochemical pregnancy rate was higherwith endometriosis (P = 0.05) but clinical pregnancy and livebirth rates did not differ between groups or in relation toantibody status. Significant differences in immunoglobulin andcomplement components occurred in women with and without successfulbiochemical pregnancy.     

Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome

BACKGROUND: Previous studies in humans and mice have suggested the importance of leptin in fetal growth. Recurrent miscarriage may be a result of abnormal placental and/or fetal development and therefore abnormal leptin levels may be associated with this form of pregnancy loss. METHODS: Leptin and leptin-binding activity (LBA) were measured in blood obtained from women who had a history of recurrent miscarriage (n = 53) during weeks 5-6 and 7-8 of pregnancy, and the concentrations were correlated with subsequent pregnancy outcome. RESULTS: Concentrations of leptin ranged from 1.4-62.8 ng/ml, but there was a strong correlation (r = 0.825, P < 0.001) between leptin values at weeks 5-6 and 7-8 in the same woman. Women who subsequently miscarried had significantly lower plasma leptin concentrations on both weeks 5-6 (13.34 +/- 2.1 ng/ml) (P < 0.05) and 7-8 (13.71 +/- 2.4 ng/ml) (P < 0.01) of pregnancy, than women who subsequently had a term birth (22.04 +/- 2.43 ng/ml week 5-6, 24.76 +/- 3.66 ng/ml week 7-8). LBA values ranged from 1-8.5% but there was no significant difference in LBA in blood obtained from women who subsequently miscarried or had a live birth. CONCLUSIONS: The significantly lower concentrations of leptin in women who subsequently miscarried suggest that leptin may play a role in preventing miscarriage. However, as there was a considerable overlap between the values of leptin in women who subsequently miscarried, and those that had a live birth, these measurements are of limited use in the prediction of pregnancy outcome in these women.     

Prospective, serial investigations of in-vitro lymphocyte cytokine production, CD62L expression and proliferative response to microbial antigens in women with recurrent miscarriage

BACKGROUND: Lymphocytes from pregnant women with unexplainedrecurrent miscarriage (RM) may be characterized by a T-helpertype 1-dominated cytokine production and a higher proliferativeresponse to microbial recall antigens compared with normal pregnantwomen. METHODS: Serial blood samples were taken from 14 womenwith RM (at least three previous consecutive miscarriages) duringthe first 14 weeks of pregnancy, and one blood sample was takenfrom 15 control women in gestational weeks 7–8. Of the14 pregnant RM patients, four produced a live birth and 10 miscarried.Lymphocytes were in-vitro-stimulated by mitogens, allogeneiccells and microbial antigens, and the production of a seriesof cytokines, the proliferative responses and lymphocytic expressionof CD62L (which may be a marker of T-helper type 2 lymphocytes)were measured. RESULTS: Repeated measurements of cytokine productionwere reproducible during the first trimester. The proliferativeresponses to herpes simplex and tetanus antigens were increased,and the ratio of CD62L–/CD62L+ expressing CD4+CD45RO+lymphocytes was decreased in patients compared with controls(P = 0.01, P < 0.01 and P < 0.01 respectively). CONCLUSION:The results of the in-vitro assays used were reproducible inserial testing during pregnancy. The importance of CD62L expressionon lymphocytes for RM and the relevance of the maternal responseto microbial antigens during pregnancy should be further explored.     

Embryo loss pattern is predominant in miscarriages with normal chromosome karyotype among women with repeated miscarriage

OBJECTIVE: The aim of this study was to assess pregnancy loss patterns in women with repeated miscarriage (RM), according to fetal chromosome karyotypes and aetiologies of RM. METHODS: In this cohort study, 168 fetal chromosome karyotypes of miscarriages were investigated. The pregnancy loss patterns were compared between 75 miscarriages from RM women who had a history of two or more consecutive miscarriages and 93 miscarriages from control women whose previous pregnancies ended in live births without a history of RM. By serial ultrasonography, embryo loss (EL) was defined as miscarriage before fetal heat movement was identified and fetal loss (FL) as miscarriage after fetal heat movement was identified. The EL rate was calculated as EL/(EL+FL). RESULTS: The EL rate (66.7%) in miscarriages with normal karyotypes among RM women (n=42) was higher (P<0.05) than that (45.7%) in controls (n=46), while the EL rate (30.3%) in miscarriages with abnormal karyotypes among RM women (n=33) did not differ from that (25.5%) in the controls (n=47). The EL rate (71.4%) in miscarriages with normal karyotypes among unexplained RM women (n=21) was much higher (P<0.05) than that in the controls. CONCLUSIONS: By evaluating fetal karyotypes, we demonstrated for the first time that EL was predominant in miscarriages with normal karyotype among RM women.     

Decidual and Placental Histologic Findings in Patients Experiencing Spontaneous Abortions in Relation to Pregnancy Order

PROBLEM: In investigating possible immunologic causes of miscarriage, we hypothesized a more frequent maternal immune response in placental tissue in women miscarrying their first pregnancy, compared to woman miscarrying following at least one full-term delivery. METHOD OF STUDY: We reviewed the medical charts of 273 consecutive women who had treatment for miscarriage. After application of the exclusion criteria, 32 patients were selected who had a full-term pregnancy outcome following the index miscarriage. The patients were divided into two groups based on the pregnancy order of the index miscarriage. Group 1 (n=16) included women who lost their first pregnancy. Group 2 (n=16) included women who miscarried a pregnancy after at least one full-term delivery. Miscarriage tissue was evaluated for placental and decidual histologic features of uteroplacental vasculopathy and chronic inflammation. RESULTS: Lesions of chronic inflammatory and uteroplacental vasculopathy were generally more common in Group 1 as compared to Group 2, and the presence of more than one of the histopathologic lesions was significantly more frequent in Group 1 (37.5%, 6/16) than in Group 2 (0/16, P=.02, Fisher's Exact). CONCLUSIONS: This study demonstrates more frequent lesions of chronic inflammation and uteroplacental vasculopathy in miscarriage patients with a first pregnancy loss, compared to those patients who have had a pregnancy loss following at least one full-term delivery.     

Immunology: Antiphospholipid antibodies and {beta}2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach

Five hundred consecutive women (median age 33 years; range 19–45)with a history of recurrent miscarriage (median 4; range 3–16)were screened for the presence of antiphospholipid antibodies(APA)-lupus anticoagulant (LA) and/or anticardiolipin antibodies(ACA). The prevalence of persistently positive tests for LAwas 9.6% and for immunoglobulin G (IgG) and immunoglobulin M(IgM) ACA was 3.3 and 2.2% respectively. Only seven women (1.4%)were LA and ACA positive. Repeat testing, after an intervalof at least 8 weeks, demonstrated that only 65.7% of LA positive,36.6% IgG ACA positive and 36.0% IgM ACA positive women on initialtesting had a second positive test result. The dilute Russell‘sviper venom time detected the LA significantly more often thaneither the activated partial thromboplastin time or the kaolinclotting time (P < 0.001). There was no difference in thegestation of previous miscarriages between APA positive andAPA negative women. There was no difference in the plasma ₂-glycoprotein-Iconcentrations between APA positive and APA negative women withmiscarriages and normal women. All women with a history of recurrentmiscarriage should be tested for the presence of both LA andACA. A second confirmatory test should be performed in thosewith an initial positive test result.     

Andrology: Strategies in frozen donor semen procreation

Data were analysed from 710 couples who had been assessed todetermine the effectiveness and the drawbacks of three differentmethods of insemination using frozen donor semen. Intracervicalinsemination (ICI) was the first method used when the womenhad no tubal disorder: 255 pregnancies were achieved in a totalof 2558 cycles (10%). Intrauterine insemination (IUI) associatedwith ovarian stimulation resulted in 152 pregnancies over 966cycles (16%). In-vitro fertilization (IVF) was proposed after12 insemination failures using either of the other methods orwhen the initial gynaecological examination had revealed abnormalitiessuch as tubal occlusions; 48 pregnancies were obtained in 262cycles (18.3%). The pregnancy rate using ICI was significantlyhigher when two inseminations were performed per cycle, comparedwith one insemination per cycle (12.3 versus 7%, P < 0.001).The number of motile spermatozoa per straw was correlated withthe pregnancy rate when using ICI, rising from 9% with <4X10⁶motile spermatozoa to 13.8% with 4–8X10⁶ and 17.2% with>8X10⁶. No relationship was found between the number of motilespermatozoa and the pregnancy rate using IUI and IVF. The incidenceof primary ovulatory disorder was higher among women whose husbandswere oligozoospermic than among those whose husbands were azoospermic(19 versus 9%, P < 0.01), but ovarian stimulation improvedthe fecundity of subfertile women. The outcome of pregnancieswas also analysed for the three methods. From these data, strategicplans have been proposed to maximize the pregnancy rate forwomen undergoing therapeutic donor insemination with frozensemen.     

Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses from women with recurrent abortion

As part of our continuing programme to investigate immunological causes of unexplained recurrent pregnancy losses, we studied subpopulations of white blood cells and their activation status in decidua of women with a history of recurrent spontaneous abortion (RSA). We differentiated specifically between normal karyotyped male fetuses and abnormal karyotyped fetuses with trisomy 16 because trisomy 16 is not compatible with life and is thus a non-controversial cause of spontaneous miscarriage. Leukocytes were counted in paraffin-embedded decidua after immunohistological staining for CD45 (LCA), CD3, CD56, CD68, CD69 and CD25. Numbers of activated versus non-activated T lymphocytes, NK cells and macrophages were compared in decidua from women with: (i) unexplained RSA who had a normal male karyotype (n = 17) miscarriage; (ii) unexplained RSA who had a trisomy 16 (n = 21) miscarriage; and (iii) normal gestationally age-matched first trimester pregnancies following elective termination procedures (n = 20). Significantly more activated leukocytes were detected in the decidua of women with unexplained RSA who had a normal male karyotype compared to the other groups (P < 0.0001). In addition, numbers of cells comprising the major leukocyte subpopulation, CD56+ NK cells, appeared reduced in the decidua of women with unexplained RSA compared to decidua from women having elective terminations. Increased numbers of activated leukocytes in the decidua of women with a history of unexplained recurrent pregnancy loss who had a normal karyotyped pregnancy provide evidence that cellular immunity may be involved in unexplained recurrent pregnancy loss.