Removal of a residual portion of a uterine septum in women of advanced reproductive age: obstetric outcome

BACKGROUND: To learn more about the obstetric outcome after initial septum resection and remnant septum (< or =1 cm) resection. METHODS: In 94 patients with septate uteri who underwent uterine septum resection, the reproductive efficiency was analysed in a prospective observational study. The reproductive outcome was analysed after initial resection and (if required) consecutive procedures. RESULTS: A total of 94 women were enrolled in the study; all had had two or more miscarriages. The septum was completely removed during the first hysteroscopy in 58 (62%) cases. A residual septum was observed in 36 (38%) patients. Subsequent operative hysteroscopy was performed in the cases (29/36; 80.5%) involving repeated miscarriage and unsuccessful conception. The minimum observation time was 24 months. The difference in delivery rate after the first hysteroscopy between those with a normalized uterine cavity (26/58; 44.8%) and those with remnants (7/36; 19.4%) was statistically significant (P < 0.05). In fact, following the normalization of the uterine cavity, 62.1% (18/29) of the patients delivered, as compared with 19.4% of those (7/36) with a residue and Kaplan-Meyer curves revealed a statistically significant difference (P < 0.05). CONCLUSIONS: Women with a remnant uterine septum have an increased chance of successful pregnancy with an improved obstetric outcome after normalization of the uterine cavity.     

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.     

A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure.

Thrombophilia was recently suggested as a possible factor in recurrent pregnancy losses. We studied prospectively 125 patients (mean age 31.4 +/- 5.6 years) with one or more first or second trimester pregnancy losses for the prevalence of activated protein C resistance (APCR). Proteins C and S antigens, antithrombin III, anticardiolipin, and lupus anti-coagulant were also evaluated. Patients with uterine malformations, hormonal abnormalities, chromosomal translocations and infectious causes were excluded. A control group of 125 women with no past fetal loss were matched with the study group. Whenever the APC-sensitivity ratio (APC-SR) was 相似文献   

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

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

Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss

BACKGROUND: The genetic predispositions to venous thrombosis such as factor V Leiden (FVL) mutation (Arg 506 Gln), prothrombin (FII) gene mutation (G20210A), and mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) have been reported to be associated with recurrent pregnancy loss. This paper examines the prevalence of markers for genetic thrombophilias in women with recurrent miscarriage. METHODS: The prevalence of FVL, FII G20210A and MTHFR C677T was compared in 108 women with three or more pregnancy losses either exclusively in the first trimester, or mixed first and second trimester losses, with the prevalence found in 82 fertile parous control women without miscarriages. Markers for the thrombophilias were assessed by PCR analysis. RESULTS: Twenty-three of the 108 patients (21.3%), had thrombophilia markers, which was similar to the proportion of patients in the control group (20.7%) with these markers. The prevalences of FVL and FII G20210A were lower in the study group than in the control group (3.7 versus 6.1% for FVL and 4.6 versus 6.1% for FII respectively); however, the difference was not statistically significant. In contrast, the prevalence of MTHFR C677T was higher in the study group than the control population (13 versus 8.5% respectively), but this difference was not statistically significant. There was no statistically significant prevalence of any particular thrombophilia in patients with previous first and second trimester pregnancy losses compared with patients with first trimester losses alone. CONCLUSION: Thrombophilia was not found to be associated with recurrent pregnancy loss.     

Prevalence of circulating procoagulant microparticles in women with recurrent miscarriage: a case-controlled study

BACKGROUND: Circulating microparticles are markers of cell activation associated with various prothrombotic states. As hypoxia due to uteroplacental thrombosis is considered to be one of the causes of pregnancy loss, microparticles may be associated with pregnancy loss, in addition to, or as part of, other procoagulant states such as antiphospholipid syndrome or hereditary thrombophilias. The objective of this study was to examine the prevalence of circulating microparticles in women with recurrent pregnancy loss. METHODS: A total of 96 women with recurrent pregnancy losses were enrolled in a case-control study and compared with 90 parous women. Microparticles were measured by flow cytometry using fluorescent anti-CD51/CD31 antibodies. RESULTS: Microparticle levels >2 SD above the mean of controls (57,700/ml) were detected in 12 out of 96 women with recurrent miscarriages (12.5%), compared with two of the 90 control women (2.2%), P<0.008. The titre of microparticles did not correlate with age, number of pregnancy losses, primary secondary or tertiary aborters status, or with pregnancy losses in the 1st or 2nd trimesters. CONCLUSIONS: A proportion of women with pregnancy loss have elevated endothelial microparticles suggesting that endothelial damage or activation might be associated with the pathogenesis of pregnancy loss.     

Antiphospholipid antibodies in 146 women with repeated pregnancy losses

Antiphospholipid antibodies are associated with arterial and venous thrombosis and recurrent abortions. However, the prevalence of these antibodies in repeated miscarriages varies in different reports. To obtain quantitative data with restricted criteria and discuss the origin of the variability on the literature, we investigated the presence of antiphospholipid antibodies in 146 women who had 2 or more consecutive pregnancy losses and in 99 women whose pregnancies were successful. Antiphospholipid antibodies (lupus anti-coagulant or anticardiolipin antibodies of 20 or more IgG units) were found in 45% of women with pregnancy losses and in 9% of controls (p < 0.001). The type of loss was determined according to the trimester of pregnancy and the time of the fetal loss. 68% of patients with antiphospholipid antibodies had at least one fetal loss on the second or third trimester compared with 45% of patients without fetal loss (p < 0.01). Further studies should be conducted using more rigorous definition of clinical and laboratory characteristics in a way to allow better comparison between studies.     

Influence of position and length of uterus on implantation and clinical pregnancy rates in IVF and embryo transfer treatment cycles

In a prospective study of 807 consecutive women shown to have an apparently normal uterus after hysterosalpingography, hysteroscopy or pelvic ultrasonography prior to IVF or intracytoplasmic sperm injection (ICSI) and embryo transfer, the position and length of the uterine cavity was measured routinely at a pre-treatment mock transfer procedure. The apparent length of the uterine cavity was <7 cm in 128 women (group 1), 7-9 cm in 594 women (group 2) and >9 cm in 85 women (group 3). The uterus was noted to be retroverted in 38. 2% (308) women. The embryo transfer catheter was advanced to 5 mm from the uterine fundus based on the previously determined cavity length in all the embryo transfer procedures at 48 h after oocyte collection. Implantation and clinical pregnancy rates were not significantly different with respect to position of the uterus, difficulties encountered in passage of the catheter, mean age of the women, aetiology or duration of infertility or embryology events. An apparently greater cavity length was seen in older and/or parous women, but the difference was not statistically significant. Although the highest implantation and clinical pregnancy rates were seen in women with a cavity length of 7-9 cm (group 2) the differences were not statistically significant: group 1, 18.9 and 36. 7%; group 2, 21.0 and 46.5%; and group 3, 17.3 and 32.9% respectively. The incidence of ectopic pregnancy per reported clinical pregnancy was highest in group 1 women, being 14.9% (7/47) in comparison with group 2 (1.8%, 5/276) and group 3 (0%, 0/27) (P: < 0.0005), suggesting that the size of the uterus is a critical factor in the aetiology of ectopic pregnancy in IVF/ICSI-embryo transfer.     

Pregnancy following treatment of symptomatic myomas with laparoscopic bipolar coagulation of uterine vessels

BACKGROUND: Laparoscopic bipolar coagulation of uterine vessels (LBCUV) has been employed for women with symptomatic uterine myomas, but its effect on subsequent pregnancy has not been characterized. METHODS: Four-hundred and twenty-three women entered the study between March 1999 and December 2001. Of these, 142 women (33.6%) were under the age of 40 years at the time of LBCUV, 36 of whom (36/142, 25.3%) were sexually active without contraception. In a prospective study of 142 patients (<40 years old) undergoing LBCUV for symptomatic myomas, 15 women became pregnant (17 total pregnancies) and were evaluated by physical and ultrasound examinations. RESULTS: The volume of the dominant myoma was 117.4 +/- 118.4 and 36.8 +/- 56.8 cm(3) before and after LBCUV respectively. Volume of the dominant myoma after pregnancy was 46.2 +/- 76.7 cm(3) (mean +/- SD). There was a significant difference in myoma volume before and after LBCUV (P = 0.002), but no significant difference in myoma volume when comparing post-partum size with post-LBCUV size (P = 0.269). Pregnancy outcomes included seven miscarriages in the first trimester and one premature rupture of membrane (PPROM). Although the other pregnancies were regarded as uncomplicated, only two women were delivered of normal neonates as the other seven pregnancies were terminated secondary to patient request. CONCLUSIONS: The pregnancy and term pregnancy rates in sexually active women without contraception were 41.6% (15/36) and 5.6% (2/36) respectively. Because a relatively high rate (7/17, 41.2%) of early miscarriages was observed, we recommend that this procedure be employed only for women who do not desire additional children.     

Clinical relevance of diagnosing structural chromosome abnormalities in couples with repeated miscarriage

BACKGROUND: The annual number of parental karyotypes in cases of repeated miscarriage is increasing gradually in The Netherlands. The efficiency of offering parental karyotyping in couples with repeated miscarriage has not been evaluated before, especially not for the group with miscarriages at advanced maternal age. METHODS: A historical cohort study and nested case-control study were conducted, including couples with at least two miscarriages. Data were retrieved from medical records and telephone interviews. The obstetric follow-up was recorded for > or =2 years after the parental chromosome analysis. Data were analysed to compare ratios of carrier/non-carrier couples in whom maternal age was > or =36 or <36 years at the second, third or fourth and more miscarriage. A projected prevalence of carrier status of a structural chromosome abnormality was calculated by extrapolating the number of included patients to the original level of the total screening population. RESULTS: Forty-one couples with carrier status of a structural chromosome abnormality and 74 couples without carrier status were included. No unbalanced offspring arose after the detection of a structural chromosome abnormality. The risk of being a carrier was not significantly lower (as might be expected) when women were > or =36 years. Ascertainment after two, three, or four and more miscarriages did not change these findings. CONCLUSIONS: Karyotyping of 1324 couples ascertained for repeated miscarriage did not yield an unbalanced fetal chromosome pattern after the ascertainment of parental carrier status. In women with advanced maternal age, the frequency of carrier status was not lower than in younger women.     

The one-stop recurrent miscarriage clinic: an evaluation of its effectiveness and outcome

BACKGROUND: Couples with recurrent miscarriages make several visits to specialized clinics for investigations before treatment is offered. Consequently, 'the interval' between receipt of referral and advice to try for a pregnancy is often lengthy. The objectives of this study were to examine the effect of a 'one-stop' clinic on 'the interval', throughput and the outcome from this clinic. METHODS: The processes for investigation, management and outcomes of 189 couples seen in our Recurrent Miscarriage Clinic (RMC) and their records were reviewed. RESULTS: The one-stop clinic reduced the interval and number of visits by 36% (206.6 to 130.4 days, P < 0.001) and by 60% (2.5 to 1, P < 0.002) respectively. The prevalence and frequency of aetiological factors were similar in those with two and three or more miscarriages (41% versus 45%, P > 0.05). The commonest aetiological factors were thrombophilias (14%) and antiphospholipid syndrome (11%). No cause was identified in 54% of cases. The pregnancy and live birth rates were best in the idiopathic group (75%), those with thrombophilias (64%) and autoimmune antibodies (83%). Older couples had the worse pregnancy rates and outcome. CONCLUSION: A one-stop clinic significantly shortens 'the interval' between referral and initiation of treatment. Investigations should be initiated in women after two consecutive miscarriages.     

Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure

BACKGROUND: The objective of this study was to determine the incidence of undiagnosed thrombophilic factors and its relation to IVF and embryo transfer failure in women who have had three or more previous IVF-embryo transfer cycles. METHODS: The study group comprised of 90 consecutive women with three or more previously failed IVF-embryo transfer cycles (group A). Two control groups were enrolled: group B (n=90) included women who have had successful pregnancy after their first IVF-embryo transfer cycle, and group C (n=100) included women who conceived spontaneously with at least one uneventful pregnancy and no previous history of miscarriage. All women were tested for the presence of inherited [factor V Leiden (FVL) mutation, prothrombin mutation, methylenetetrahydrofolate reductase (MTHFR) mutation and deficiencies in proteins S and C and antithrombin III] or acquired (lupus anticoagulant and anticardiolipin) thrombophilic factors. RESULTS: An increase in the incidences of FVL, MTHFR and antiphospholipid antibodies was found in the study group compared with the two control groups. At least one inherited or acquired thrombophilic factor was detected in 68.9% of women with repeated IVF failure compared with 25.6 and 25% in the groups B and C, respectively (P<0.01). Combined thrombophilia (two or more thrombophilic factors) was significantly higher in women who have had repeated IVF failure as compared with the two control groups (35.6 versus 4.4 and 3%) (P<0.0001). CONCLUSION: Thrombophilia has a significant role in IVF-embryo transfer implantation failure. Women with repeated IVF-embryo transfer failure should be screened for thrombophilia.     

Modern surgical approaches to female reproductive tract

Laparoscopic and hysteroscopic surgery have changed the management of many gynaecological disorders. Procedures that previously required a long duration of hospitalization can now be done on an outpatient basis or with a short hospital stay. Surgical treatment remains the definitive and universal treatment of ectopic pregnancy and it can be safely done by laparoscopy. Most reproductive operations are done by laparoscopy and the results appear to be similar to those obtained with laparotomy. Those needing a laparotomy will be better treated by in-vitro fertilization. Laparoscopic ovarian drilling is a viable alternative for infertile women with polycystic ovarian syndrome. Most ovarian cysts and endometriosis should be treated by laparoscopy. Although uterine myomas can be removed by laparoscopy, the uterine integrity after the procedure is questionable. Surgery should be reserved for women who have completed their family or those with pedunculated or shallow intramural myomas. Alternatively, a laparoscopically assisted myomectomy can be done. For laparoscopic hysterectomies for benign lesions, supracervical hysterectomy appears to be a good option. Hysteroscopy has changed our management, particularly for abnormal uterine bleeding. A submucous myoma and polyp can be removed by hysteroscopy and, as an alternative to hysterectomy, endometrial ablation can be done. In the future, most procedures will be done by endoscopy and laparotomy will be reserved only for selected cases.     

Strong evidence that skewed X-chromosome inactivation is not associated with recurrent pregnancy loss: an incident paired case control study

BACKGROUND: Previous studies have reported conflicting results regarding recurrent pregnancy loss and skewed X-chromosome inactivation. Hence, we sought an association by carrying out a specifically designed incident paired case-control study with required statistical power. METHODS: Design incident 1:3 matched case-control study, from 2003 to 2007. Setting: University Hospital of Brest. Patients: Women, from the Brittany area, consecutively referred for at least two unexplained consecutive spontaneous abortions. Controls: Women from the same geographic area, with no history of pregnancy loss and at least one normal pregnancy, recruited using electoral lists and then paired with cases, with respect to age, to within 1 year. Intervention: Assessment of skewed X-chromosome inactivation. Statistical analysis: Comparison of the ratio of >90% skewed X-chromosome inactivation by conditional logistic regression. RESULTS: Five hundred and forty-three controls (mean age: 34.3 years) were paired within 1 year to 200 cases. The cases (mean age: 33.6 years) had experienced between 2 and 14 consecutive losses (median 3). The rate of >90% skewed X-chromosome inactivation was not statistically different (P = 0.33, odds ratio: 0.58, 95% confidence interval: 0.19-1.77) between cases and paired controls, 2.27% versus 4.1%, respectively. CONCLUSIONS: We conclude that there is no association between skewed X-chromosome inactivation and recurrent pregnancy loss, defined as two or more unexplained consecutive spontaneous abortions.     

The value of hysteroscopic evaluation in patients with preclinical in-vitro fertilization abortions

The study was conducted on 144 women who experienced preclinicalabortions, i.e. a transitory rise in -human chorionic gonadotrophin(HCG) without any clinical or sonographic evidence of pregnancy,to identify the relationship between preclinical abortions andintrauterine pathology. Hysteroscopy was performed 1–2weeks after the decline of -HCG concentrations to negative values.Intrauterine adhesions were detected in three patients (2.1%),most of these being of the mild type. Concomitant intrauterineabnormalities, mainly uterine septa, were found in 14 (9.7%)cases. We believe that preclinical abortions do not predisposeintrauterine adhesions and curettage is superfluous. An incompleteuterine septum seems to be the major factor predisposing thisearly pregnancy wastage. Hysteroscopy following this conditionis an easy and efficient means for both identifying intrauterinepathology and excluding adhesions.     

Evaluation of uterine cavity by sonohysterography in women scheduled for intracytoplasmic sperm injection

A prospective study was performed to determine the feasibility of evaluating the uterine cavity by sonohysterography (SHG) in women who were scheduled for intracytoplasmic sperm injection (ICSI) due to severe male factor infertility and who had not had a previous hysterosalpingography (HSG). Sonohysterography was performed in 80 women scheduled for ICSI. A subsequent hysteroscopy was undertaken in patients with intracavitary lesions. The outcome of ICSI for the women undergoing SHG was compared with that of 240 cycles performed (during the same time period) in patients who had a normal HSG before admission to the clinic. There were no complications attributable to the SHG procedure. Hysteroscopy correctly identified all lesions depicted by SHG. SHG and HSG groups were comparable with regard to female age and duration of infertility. Clinical pregnancy rates per transfer were 40.2% and 42.5% in the SHG and HSG groups, respectively. Abortion rates in the two groups were also similar (14.8 and 11.0%, respectively). In conclusion, sonohysterography appears to be a simple, inexpensive, and safe alternative to HSG for evaluation of the uterine cavity in women scheduled for ICSI.      

Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses

BACKGROUND: Low levels of mannose-binding lectin (MBL) predispose to various infectious and inflammatory disorders and have been reported to be associated with recurrent early miscarriages. Recurrent late pregnancy losses (RLPL) in the second trimester is a rare but devastating syndrome where maternal rather than fetal causes are likely to play a stronger role than in early recurrent miscarriage. METHODS: We identified 75 patients with at least two late losses of pregnancies with apparently normal fetuses between gestational week 14 and 30 among patients with recurrent pregnancy losses referred to our clinic. Polymorphisms in the MBL2 gene associated with plasma MBL levels were investigated in all patients and in 104 women with two or more children and no miscarriages. The patients were divided into three groups: one with clinical signs of cervical insufficiency, one positive for the lupus anticoagulant (LAC) and an idiopathic group. RESULTS: Among all patients with RLPL, 26.7% had MBL2 genotypes associated with MBL deficiency compared with 12.5% in controls [odds ratio (OR) 2.55; 95% confidence interval (CI) 1.17-5.52; P < 0.02]. Among patients with clinical signs of cervical insufficiency or the LAC, the frequency of genotypes associated with MBL deficiency was not significantly increased. However, among 38 patients with idiopathic RLPL, 36.8% carried low-producing MBL2 genotypes, which was significantly more than in controls (OR 4.08, 95% CI 1.70-9.83, P = 0.001). CONCLUSIONS: MBL deficiency is strongly associated with idiopathic RLPL. This may point towards a role for excessive inflammatory disturbances as a cause of the syndrome.     

Antiphospholipid antibodies in infertile couples with two consecutive miscarriages after in-vitro fertilization and embryo transfer.

Of 682 women who had undergone in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with embryo transfer, 84 were successful on two occasions, with 16 of these resulting in miscarriage before 20 completed weeks. Antiphospholipid antibodies (APA) were estimated by enzyme-linked immunosorbent assay in these women (group 1) and compared to two control groups: 42 fertile women with three or more miscarriages (group 2) and 60 women with primary infertility undergoing IVF or ICSI (group 3). An apparently higher prevalence of seropositivity was seen in group 1 women (25%) compared to the group 3 women (6.6%) and it was similar to that seen in group 2 women (21.4%). Therefore the recommendation that women with two consecutive miscarriages after IVF or ICSI should have APA estimations performed routinely may be justified.     

The prognostic value of anti-paternal antibodies and leukocyte immunizations on the proportion of live births in couples with consecutive recurrent miscarriages

Anti-paternal antibodies directed towards paternal leukocytes have been used to predict the prognosis for the subsequent pregnancy in women with consecutive recurrent miscarriages (CRM) and also to determine if the patient has become immune after paternal leukocyte immunization. The predictive value is controversial, as these antibodies are not essential for pregnancy to develop, and only occur in a minority of parous women. This study tried to determine the predictive value of these antibodies when assessed separately for women with five or more abortions and compared to women with three or four abortions. The patients were assessed separately so that the higher live birth rate in the latter group would not obscure meaningful results in the former group with a poor prognosis. Antibody production, whether spontaneous, or induced by immunization, raised the live birth rate in primary and tertiary aborters with three, four, five or more abortions. Anti-paternal antibodies increased the proportion of live births from 18.5 to 53. 7% (P /= 5 CRM and 3-4 CRM respectively. Both immunization with paternal leukocytes per se and the ability to express anti-paternal antibodies were associated with an increased proportion of live births in the next pregnancy. Multivariate analysis showed that that the odds ratio for a live birth was approximately four times greater in women who were immunized and produced anti-paternal antibodies than in control patients. The lack of anti-paternal antibodies at initial testing could serve as a marker for the benefit of immunization with paternal leukocytes; the subsequent presence as a prognostic marker for the subsequent pregnancy.     

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.