Embryo donation families: mothers' decisions regarding disclosure of donor conception

BACKGROUND: Previous data suggest that parents who adopt a child tend to support full disclosure while donor conception families prefer to keep the method of conception relatively private. It is not known whether parents in embryo donation families will tend towards the adoption model, therefore, we studied families with a child conceived using donated embryos. METHODS: A total of 21 embryo donation families with a child aged 2-5 years were recruited through UK fertility clinics. Mothers were administered a standardized semi-structured interview, obtaining data on the extent of their disclosure to children and other family members and their reasons for this decision. RESULTS: At the time of interview, 9% of mothers had told their child how they had conceived; 24% of mothers reported that they were planning to tell the child in future; 43% had decided that they would never tell the child, and the remaining 24% were undecided. However, nearly three-quarter of mothers (72%) had disclosed to other family members. Maternal grandparents were more likely to have been told than paternal grandparents (P < 0.025). Reasons cited for non-disclosure to the child included the desire to protect the child, the belief that disclosure is unnecessary, and the concern that family relationships would be damaged. Reasons in favour of disclosure included the desire to avoid accidental disclosure and the belief that the child has the right to know. CONCLUSIONS: Embryo donation mothers were similar to parents of donor insemination and oocyte donation children in their attitudes towards disclosure of donor conception.     

A report on 100 cycles of oocyte donation; factors affecting the outcome

Eighty-two patients had 100 cycles of oocyte donation from 68 donors resulting in 27 clinical pregnancies. The source of donated oocytes was 42 fertile volunteers and 26 patients from the assisted conception programme. The pregnancy rate was significantly higher when intra-Fallopian transfer was performed (36%; 21/59), compared with intrauterine transfer (15%; 6/41). The pregnancy rate following fresh gamete/embryo transfer (39%; 15/39) was slightly higher than for frozen embryo transfer (20%; 12/61). The age of the recipient significantly affected the pregnancy rate. The pregnancy rate was 50% in the 25-29 years age group and steadily dropped to 9.7% in the 45-49 age group. The pregnancy rate in patients with primary ovarian failure (50%; 8/16) was significantly higher than in patients with secondary ovarian failure (18%; 9/50). The pregnancy rate was significantly greater when parous donors (33%; 23/69) were used compared with non-parous donors (13%; 4/31). The number of gametes/embryos transferred significantly affected the pregnancy rate regardless of the treatment used. If one or two gametes/embryos were transferred, the pregnancy rate was 11% compared with 33% if three to four embryos were transferred. The age of the donors did not affect the pregnancy rate. The majority of the donors were under the age of 35 years. The best results (50% per cycle) were therefore achieved using gametes from parous donors and transferring three to four oocytes fresh to the Fallopian tubes of a young recipient.     

Long-term sexual co-habitation offers no protection from hypertensive disease of pregnancy

Long-term sexual co-habitation and previous pregnancies are thought to protect against the development of hypertensive disease of pregnancy. In order to test the hypothesis that pregnancies conceived after prolonged exposure to the partner's spermatozoa have reduced rates of hypertensive disease this study examined the outcomes of pregnancies of women who conceived by donor insemination as compared with women who conceived after IVF with partner's spermatozoa. This was a retrospective cohort study of 218 women attending an IVF clinic, 45 of whom conceived by donor insemination and 173 of whom conceived by partner's spermatozoa. Cases were identified from the IVF unit and data were extracted from patients' notes by blinded observers. Results showed no difference between the groups, with 22% of women who conceived with donor spermatozoa and 24% who conceived with partner spermatozoa developing some form of hypertensive disease of pregnancy. Insemination by partner's spermatozoa was not associated with a reduction of hypertensive disease and neither was donor spermatozoa associated with an increased incidence.     

Turner's syndrome and pregnancies after oocyte donation

A total of 20 clinical pregnancies was achieved among 18 women with Turner's syndrome who were treated in an oocyte donation programme. The oocytes were donated by voluntary unpaid donors. A mean of 1.8 embryos per transfer was given to each recipient by way of 28 fresh and 25 frozen embryo transfers. With fresh and frozen embryos, 13 and seven pregnancies respectively were achieved. The clinical pregnancy rate per fresh embryo transfer was 46%, and the implantation rate 30%, being similar to the corresponding rates among our oocyte recipients with primary ovarian failure in general. The corresponding rates with frozen embryos were 28 and 19%. Of these pregnancies, 40% ended in miscarriage. This high rate may be explained by uterine factors. Six women were hypertensive during pregnancy, a rate comparable with that in other oocyte donation pregnancies. All these women delivered by Caesarean section. Pregnancy and implantation rates after oocyte donation were high in women with Turner's syndrome, but the risk of cardiovascular and other complications is high. Careful assessment before and during follow-up of pregnancy are important. Transfer of only one embryo at a time to avoid the additional complications caused by twin pregnancy is recommended.     

Cyclic corticosteroid immunosuppression is unsuccessful in the treatment of sperm antibody-related male infertility: a controlled study.

In this double blind cross-over study, 20 infertile men, who had sperm antibodies detected by the mixed antiglobulin reaction (MAR test) in the ejaculate and by the tray agglutination test (TAT) in serum, were treated with 40 mg/day prednisolone or placebo from days 1 to 10 of the partners' menstrual cycle. Patients were randomly allocated to different treatment groups. While group 1 started with placebo followed by verum for three consecutive cycles, group 2 began with verum and continued with placebo. All patients had regular intercourse (n = 19) or intra-cervical insemination at ovulation (n = 1). A post-coital test or a sperm penetration test was performed during verum and placebo regimes. Blood samples were drawn from the male partner at this time to control the efficacy of prednisolone treatment by checking the TAT titre. No pregnancy occurred during prednisolone or placebo treatment. In eight of 12 patients, post-coital testing showed little improvement and antibody titres decreased in seven of 16 patients. Side-effects from medication were reported by eight patients (seven verum and one placebo cycle) and caused treatment to be discontinued in two cases. Five patients' partners conceived at a later stage by intrauterine insemination with spermatozoa prepared by 'swim up' (n = 3) or by in-vitro fertilization (IVF n = 2). Thus high dose corticosteroid therapy was ineffective in achieving pregnancies induced by infertile men positive for antisperm antibodies. Since side-effects of corticosteroids should not be underestimated in otherwise healthy men, other reproductive techniques such as intrauterine insemination or IVF should be offered to such couples.     

Termination of pregnancy after conception with donor oocytes and donor spermatozoa: case report

Two couples, each suffering from longstanding primary subfertility due to severe oligoasthenoteratozoospermia in the male partner and perimenopause in the female, were referred to Bourn Hall Clinic for assisted conception treatment. Both couples received independent counselling prior to being accepted onto our programme. Both women conceived following embryo transfer. The embryos were created from (separate) donor oocytes and donor spermatozoa, and three and two embryos were transferred respectively. The first recipient conceived a triplet pregnancy, while the second conceived a twin pregnancy. Both felt unable to cope with their multiple pregnancies and declined further counselling. Both were offered elective fetal reduction; however, both declined and both decided to terminate their pregnancies. Both patients underwent termination of pregnancy, despite being advised against it. The reasons couples may opt for termination of their much-wanted pregnancies, after a protracted period of infertility, intensive and expensive infertility treatment and despite the counselling they receive before, during and after their treatment, are discussed.     

The "vanishing embryo" phenomenon in an oocyte donation programme

BACKGROUND: We studied the incidence of vanishing embryos (VE) in pregnancies achieved by oocyte donation and evaluated the obstetric and perinatal complications. METHOD: A retrospective study was carried out based on a chart review of 399 patients with multiple pregnancies from our oocyte donation programme. We defined vanishing phenomenon as the early resorption, in the first trimester, of one or more embryos in a multiple gestation, after confirming embryonic heart activity by transvaginal ultrasound. RESULTS: Vanishing embryo was observed in 75 patients (18.8%). In 60 patients (80%) this phenomenon occurred before the ninth gestational week. A higher incidence of VE was observed in patients who initially showed a higher number of gestational sacs (P < 0.03). Vaginal bleeding in the first trimester was significantly higher in patients with VE (P < 0.005). Miscarriage rate was similar in pregnancies with and without VE (P = NS). The incidence of pregnancy induced hypertension was decreased in the group with VE (P < 0.03). Preterm spontaneous rupture of membranes occurred more frequently in pregnancies with VE (P < 0.05). However, gestational age at delivery was similar in the group with VE and the controls. CONCLUSIONS: The high incidence of VE in pregnancies achieved by oocyte donation should be considered when counselling patients with high order multiple gestations.     

Pregnancies after oocyte donation in women with ovarian failure caused by an inactivating mutation in the follicle stimulating hormone receptor.

BACKGROUND: An inactivating point mutation (Ala189Val) in the FSH receptor (FSHR) causes primary ovarian failure. It has not been known if FSH action is necessary during pregnancy and childbirth. METHODS: In 1991-2001, donated oocytes were used to treat the infertility of 12 women with ovarian failure due to this mutation. RESULTS: When 30 fresh and 15 frozen-thawed embryo transfers were performed, 14 clinical and two biochemical pregnancies resulted. To date, 12 children have been born to eight women, while one pregnancy ended in miscarriage. Three women had twin pregnancies, and one woman has delivered twice. Additionally, there are three ongoing pregnancies, of which two are second pregnancies of women who previously had a normal delivery after similar treatment. In all, 10 out of the 12 women became pregnant. Two deliveries were by Caesarean section. The rate of complications was comparable with that in pregnancies resulting from oocyte donation in general. CONCLUSIONS: Achieving and undergoing a successful pregnancy is possible when FSH action is severely decreased. Oocyte donation is an effective infertility treatment for women with FSHR mutations.     

Sperm treatment with extracellular ATP increases fertilization rates in in-vitro fertilization for male factor infertility

Previous work from our laboratory has revealed that extracellular ATP is a rapid and potent activator of human sperm acrosome reaction and fertilizing ability. In the present study, we assessed the effects of in-vitro sperm incubation with ATP on fertilization and embryo development in couples undergoing in-vitro fertilization (IVF) for male factor infertility. Oocytes from 22 women undergoing ovulation induction were divided in two groups and inseminated in vitro either with selected spermatozoa from the corresponding partner suffering from male factor infertility pre-incubated with ATP (2.5 mM) for 1 h, or with spermatozoa incubated with 0.9% NaCl solution (control group). After insemination, fertilization was assessed by the presence of pronuclei and then by embryo cleavage. The fertilization rate in the group of oocytes inseminated with ATP-treated spermatozoa improved significantly with respect to the control group (65.7 versus 42.5%, P < 0.01). No significant differences were observed in embryo cleavage and embryo quality. Embryos from both treated and control groups were transferred together in 20 transfer procedures, and in two couples fertilization was not obtained. Nine pregnancies occurred: one biochemical, one miscarriage, and seven patients delivered 9 healthy babies. Two pregnancies were twin with an overall pregnancy rate of 40.9% per cycle and of 45% per transfer. In conclusion, the results of the present study demonstrate that, in humans, extracellular ATP induces a significant increase of sperm fertilizing potential, as these findings are a rationale for the use of ATP for in-vitro treatment of human spermatozoa during IVF.     

Attitudes of donors and recipients to gamete donation

An anonymous questionnaire was circulated at two gamete donation clinics to survey the attitudes of donor insemination patients (n = 71; 89% response rate), sperm donors (n = 52; 85% response rate) and ovum donors (n = 5; 63% response rate) to the release of medical records with non-identifying information, or with identifying information of the donor involved. The majority of established sperm donors agreed to the release of medical records with or without identifying information. In the subset of potential sperm donors 85% would not enter a sperm donation programme unless anonymity was maintained, but 60% would agree to the release of non-identifying medical records. Sixty per cent of recipients of donated spermatozoa would agree to the release of medical records with identifying information of the donor, but 85% stated that they would not tell their children of their genetic origin. There is a significant difference between the attitudes of potential sperm donor recruits to these questions and those of established donors and recipients of donated spermatozoa. In conclusion, the results of this survey show that although established sperm donors would continue to donate spermatozoa if their status of anonymity was withdrawn, recruitment of new donors would be significantly reduced. This would be to the detriment of gamete donation programmes and to the subfertile couples who request this form of treatment.     

Comparative birth weights of singletons born after assisted reproduction and natural conception in previously infertile women

BACKGROUND: The possible interference of assisted reproduction techniques (ART) with epigenetic reprogramming during early embryo development has recently sparked renewed interest about the reported lower birth weight among infants born as a consequence of infertility treatments. However, the latter finding so far has relied on the comparison of the birth weight of infants conceived with ART to general population data. A more appropriate comparison group should involve pregnancies in infertile women after natural conception. Therefore, we compared neonatal birth weight data of infants born after various ART treatments, including intrauterine insemination (IUI), with those of previously infertile women achieving pregnancy after sexual intercourse. METHODS: Between August 1996 and March 2004 the data of all infertile women presenting in the infertility unit of the University Women's Hospital of Basel, Switzerland, were collected prospectively, adding up to 995 intact pregnancies and deliveries. The birth weight of all infants resulting from 741 singleton pregnancies were analysed with regard to the patients' characteristics, the occurrence of complications during pregnancy and the type of infertility treatment with which the pregnancies were achieved. RESULTS: Comparison of duration of pregnancy and birth weight of infants born after infertility treatment confirms a shorter pregnancy span and a lower mean birth weight in infants born after IVF and ICSI. If women with pregnancies after ART deliver before term, neonatal birth weight is significantly lower. CONCLUSIONS: There is a specific effect of ART, mainly IVF and ICSI, on both shortening the duration of pregnancy and lowering neonatal birth weight. Both these parameters seem to be interrelated consequences of some modification in the gestational process induced by the infertility treatment. Freezing and thawing of oocytes in the pronucleate stage had a lesser impact on pregnancy span and on neonatal birth weight.     

Slow release intrauterine insemination versus the bolus technique in the treatment of women with cervical mucus hostility.

Thirty-eight infertile women with cervical mucus hostility were divided at random into two groups for intrauterine insemination with prepared husband's semen. Eighteen women started with slow release (treatment A) and 20 with bolus (treatment B) intrauterine insemination in a cross-over study for four alternating cycles. Insemination was timed 30-36 h after a positive luteinizing hormone (LH) surge or injection of 5000 IU of human chorionic gonadotrophin, given at a follicular diameter of 18 mm during ultrasonically monitored, unstimulated cycles. A Grasby auto-syringe driver (type MS16) was used for the slow release intrauterine insemination to deliver 50 x 10(3) motile spermatozoa every minute for 3 h. Bolus intrauterine insemination was performed by deposition of 0.6 ml of prepared semen without changing the count from the swim-up portion of the washed spermatozoa. A total of 13 patients conceived, nine from 60 cycles of treatment A and four from 66 cycles of treatment B (chi-squared = 2.7143, P less than 0.05 using one-tailed statistics).     

S100B protein expression in the amnion and amniotic fluid in pregnancies complicated by pre-eclampsia

Our aim was to investigate the expression of S100B protein in the amnion and to assess the amniotic fluid concentration in pregnancies complicated by pre-eclampsia. Samples were obtained from women who developed pre-eclampsia (n = 7), pre-eclampsia with intrauterine growth retardation (IUGR) (n = 4), normotensive IUGR (n = 7) and gestational hypertension (n = 4) during pregnancy and healthy controls who delivered at term (n = 35). To determine the difference in the expression of S100B in the amnion, we performed immunohistochemistry, western blot analysis and RT-PCR. Using enzyme-linked immunosorbent assay (ELISA), we assessed the S100B concentration in amniotic fluid. The S100B mRNA expression in the amnion of pre-eclamptic patients and patients with pre-eclampsia with IUGR was significantly higher than that in the control. The amniotic fluid S100B protein concentration of the pre-eclampsia and normotensive IUGR cases was significantly higher than that of the control. This study shows that amnion could be a source responsible for the increased concentration of S100B in amniotic fluid. In pre-eclampsia, reactive oxygen species (ROS) are generated by oxidative stress. Some pathological conditions that develop during pregnancy and are related to hypoxic stress can affect the elevation of S100B concentration in the amnion.     

A programme of semen cryopreservation for patients with malignant disease in a tertiary infertility centre: lessons from 8 years' experience

The improved survival in recent years of young males suffering from cancer, and an understanding of the gonadotoxic effects of chemotherapy treatment, have motivated patients and clinicians to preserve fertility potential before embarking on adjuvant therapy. Among 231 men (mean age 28.0; range 15-56 years) diagnosed with malignant disease and referred to our unit for semen cryopreservation, 112 patients (49.8%) had reduced sperm quality of <10 x 10(6) motile spermatozoa per ejaculate; however, most had sufficient suitable spermatozoa for freezing. In 40 patients (17.3 %) the semen samples were not frozen because of complete azoospermia (n = 32) or only immotile sperm in the ejaculate (n = 2), while six men were unable to produce a single sample. Some 79 men had testicular tumours (group I), 121 suffered from haematological malignancy (leukaemia or lymphoma; group II), and 27 had cancer of different causes (group III). Men in group I had significantly lower (P < 0.001) sperm quality compared with groups II and III. There was no difference between patients with seminoma and non-seminoma tumours. In the haematological malignancy group there was no difference in sperm parameters between leukaemia (n = 12) and lymphoma (n = 77) patients, but patients with Hodgkin's lymphoma had significantly lower sperm quality compared with non-Hodgkin's lymphoma. Following chemotherapy, six couples attended the clinic for assisted conception treatment using the frozen semen. Two had successful intrauterine insemination cycles which each resulted in delivery of a healthy girl; one couple had conceived in their first in-vitro fertilization (IVF) attempt, followed by delivery of healthy twins. Two women conceived after intracytoplasmic sperm injection treatment and the sixth woman achieved only biochemical pregnancy after numerous IVF and frozen embryo replacement cycles. We recommend that a properly designed programme for semen cryopreservation for cancer patients should be developed in leading tertiary assisted conception centres, which have adequate facilities and experience for cryopreservation and can offer the whole range of appropriate assisted reproductive treatment and counselling.      

Oocyte donation in patients with Turner's syndrome: a successful technique but with an accompanying high risk of hypertensive disorders during pregnancy

BACKGROUND: Few data are available on pregnancy rate and obstetrical outcome after oocyte donation in Turner's syndrome patients. We conducted a retrospective analysis on the outcome of this subgroup. METHODS: Thirty oocyte donation cycles with fresh embryo transfer were performed in 21 patients between 2001 and 2004. RESULTS: The mean (+/-SD) age of the recipients was 33.1+/-1.8 years. The median (range) number of transferred embryos per cycle was two (1-4). Seventeen pregnancies were obtained (57%), of which 12 were clinical (40%). The implantation rate and the ongoing pregnancy rate were 22% (15 out of 68) and 30% (nine out of 30), respectively. Premature delivery was observed in 50% (four out of eight) of the pregnancies and intrauterine growth retardation in 55.5% (five out of nine) of the fetuses. Hypertensive disorders occurred in five out of eight pregnancies (three pre-eclampsias). CONCLUSIONS: Turner's syndrome patients achieve acceptable pregnancy rates after oocyte donation. A high rate of pregnancy-associated hypertensive disorders was observed which have led to a high rate of prematurity and intrauterine growth restriction. Although the number of cases in this study is limited, these results call for the need for intensive surveillance of such pregnancies. In order to reduce the risk of hypertensive disorders induced by multiple pregnancies, single embryo transfer should be proposed.     

Intrauterine insemination with spermatozoa recovered from the aspirate of artificial spermatocoele

Congenital absence of both vas deferens accounts for approximately 10% of cases of obstructive azoospermia. The purpose of the present study was to develop a treatment protocol for a group of azoospermic patients using surgical implantation of alloplastic spermatocoele to enable repeated sperm cell aspiration. Nine patients with congenital absence of both vas deferens, two with obstructed and one with destroyed vas, underwent surgery for the implantation of an alloplastic spermatocoele. In 10 of the 12 patients, vital spermatozoa were recovered from the aspirate and used for intrauterine insemination of their female partners with induced ovulation, some of whom then conceived.     

Immunology: Repeat trials of oocyte donation to women with previous donor oocyte success

Oocyte donation has proven to be highly successful in establishingpregnancy in functionally agonadal women. Both implantationand ongoing pregnancy rates in women using this method havesurpassed those normally seen in standard in-vitro fertilization(IVF) patients. Over a 5 year period, seven women who had previouslyconceived using oocyte donation elected to attempt pregnancyand deliver a second child using the same donor. In each casethe paramount consideration was to provide a sibling of thesame genetic make-up as the child or children previously borne.Of the seven women studied, whose ages ranged from 24 to 44years, five became pregnant on subsequent cycles. The time toconception varied from one to a maximum of three attempts withthree of the five women becoming pregnant on the first cycleand two requiring three cycles to establish the subsequent pregnancy.The overall rate of success in this group was 12 pregnanciesin 20 cycles of embryo transfer (60%). An exaggerated implantationrate (25.6%) was also noted (23 individual embryo implantationsfrom 90 embryos transferred). Of the 12 pregnancies establishedin these seven women, four (33%) were multiple gestations (threetriplets, one twin). We conclude that women who have previouslyexperienced pregnancy following oocyte donation are highly likelyto conceive in a subsequent trial at a rate that may be higherthan that normally seen in the general population of women undergoingoocyte donation.     

Decisions for the fate of frozen embryos: fresh insights into patients' thinking and their rationales for donating or discarding embryos

BACKGROUND: In the final decision for the disposition of unused IVF embryos patients must choose between options involving either donation or destruction, and this decision must be made in a context where there is tension about the status of embryos (i.e. whether viewed as potential children or as a base for further development) and whether embryo donation is adoption or tissue donation. This study explored the emotive experience of making a decision for either the destruction or donation of unused embryos. METHODS: Thirty-three patients (9 women and 12 couples) who discarded embryos and 15 (7 women and 4 couples) who donated embryos were interviewed. Interview data were analysed with particular attention to elements of moral deliberation and use of analogy. RESULTS: Adoption and tissue donation metaphors were both identified, and further, a metaphor of pregnancy termination was identified and found to be highly influential in the decision to donate embryos. Contrary to the majority of current evidence, this study found that participants who discarded embryos emphasized the adoption metaphor while embryo donors emphasized the metaphor of pregnancy termination. For each group the decision was driven by awareness of the option they did not want. CONCLUSIONS: The pregnancy termination metaphor emerged as morally relevant and this holds implications for defining and discussing embryo discard in counselling and consent processes.     

Obstetric and perinatal outcome of pregnancies after intrauterine insemination.

The main aim of this study was to evaluate the obstetric and perinatal outcome of pregnancies after intrauterine insemination (IUI) with the partner's spermatozoa combined with ovarian stimulation. Information concerning the antenatal care and obstetric and perinatal outcome of IUI pregnancies (n = 111), spontaneous (n = 333) and in-vitro fertilization (IVF) (n = 333) was obtained from the Finnish Medical Birth Register (MBR). The multiple birth rate in the IUI group was 17% (19/111). Significantly less antenatal care was required by the IUI group than the IVF group. The frequency of Caesarean section was 25% for IUI singletons and 58% for IUI multiples, similar to the other groups. The mean (SD) gestational age for IUI singletons at birth was 39.5 (1.8) weeks, with a mean birth weight of 3285 (575) g, compared with 3448 (600) g in non-assisted singletons (P < 0.05). For IUI multiples the mean gestational age at birth was 36.0 (2.8) weeks and the mean birth weight was 2449 (678) g. The incidence of preterm birth, low birth weight or low Apgar scores and the need for neonatal care were similar in all groups. One case of major malformation and two perinatal deaths were recorded in the IUI group. In conclusion, IUI treatment did not appear to increase obstetric or perinatal risks compared with matched spontaneous or IVF pregnancies. Most problems were associated with patient characteristics and multiple pregnancy. Reduction of the high incidence of multiple pregnancies after assisted reproductive technology is essential to improve its outcome.     

Serum inhibin A and activin A are elevated prior to the onset of pre-eclampsia

Serum inhibin A and activin A concentrations increase in pre-eclampsia. We investigated the time courses of the changes in relation to the onset of the maternal syndrome and if their measurement could be useful for clinical prediction particularly in relation to early onset disease, the most severe of the clinical presentations. Serial samples were taken from 1496 healthy nulliparae. Changes in activin A and inhibin A were analysed in women with: early onset pre-eclampsia (n = 11), pre-eclampsia delivering at 34-36 weeks (n = 14), term pre-eclampsia (n = 25) and gestational hypertension (n = 25); and in a subset with uncomplicated pregnancies (n = 25). Serum inhibin A and activin A were increased in all groups prior to pre-eclampsia, before 20 weeks in those with early onset pre-eclampsia. Screening efficacy was determined at 15-19 and 21-25 weeks in all women who developed pre-eclampsia (n = 70) and randomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for early onset pre-eclampsia: 67 and 44% at 15-19 weeks and 89 and 89% at 21-25 weeks for inhibin A and activin A respectively. Hence, serum inhibin A and activin A concentrations increase before the onset of pre-eclampsia at gestational ages that depend on when pre-eclampsia develops. On their own such measures are unlikely to prove efficient for screening.