Is there a real risk of transmitting variant Creutzfeldt-Jakob disease by donor sperm insemination?

Although >99% of cases of Creutzfeldt-Jakob disease (CJD) are caused by spontaneous or inherited mutations in the prion protein, 'variant' CJD (vCJD) arose from dietary exposure to meat products infected with the bovine spongiform encephalopathy prion. While European and Canadian sperm donor candidates are rejected for significant CJD risk factors, American sperm donors are managed like blood donors (excluding all men who spent > or =3 months in the UK during 1980-1996 or > or =5 years in Europe since 1980), even though no evidence exists for sexual transmission of prion disease. This study surveyed international experts on either prions/prion disease or donor sperm/cryobanking as to the risk of vCJD transmission via semen/donor spermatozoa (45/104 replied). Consensus expert opinion was that the risk of transmission was <1:10,000,000, even for UK men, hence ultra-conservative risk avoidance would have minimal impact on public safety. Defining 'high vCJD risk' should be based on knowledge rather than fear, and due caution founded upon quantifying real risks rather than avoiding theoretical risks. Women seeking treatment using donor spermatozoa should be allowed to judge the negligible risk of vCJD infection in comparison with acceptable everyday risks, and given the choice of accepting spermatozoa from donors screened according to European-style criteria.     

Effects of maternal body mass index on pregnancy outcome after 8570 artificial insemination cycles with donor’s sperm

Abstract

Increased body mass index (BMI) might have an adverse effect on pregnancy. However, the influence of BMI on the pregnancy outcomes after artificial insemination with donor’s sperm (AID) had been rarely reported. This study aimed to investigate the correlation between BMI and AID. The pregnancy outcome of 8570 AID cycles was retrospectively analyzed. BMI was categorized as underweight (<18.5?kg/m²; group A), normal weight (18.5–23.9?kg/m²; group B), overweight (24–27.9?kg/m²; group C), and obese (≥28?kg/m²; group D). The results showed that cumulative pregnancy rate and cumulative live birth rate in groups A, B, C and D tended to decrease as BMI increased; however, abortion rate, and ectopic pregnancy rate in groups A, B, C, and D exhibited a gradual increase in the tendency. Cesarean delivery rate also increased as BMI increased. Birth defect rate in the group D were significantly higher than that in the group A. Interestingly, the pregnancy rate was gradually decreased with increasing age in groups A, B, and C, but this was not observed in the group D. The findings suggested that BMI can affect the pregnancy outcomes after AID; it is important to achieve a normal BMI prior to AID treatments.     

Is sperm donor karyotype analysis necessary?

A case study involving four female patients inseminated with sperm samples from the same donor is reported. Routine amniocentesis of one of the patients revealed that the fetus is a carrier of a balanced reciprocal translocation, 46,XY,t(1;10)(q12;q11.2), which was subsequently detected in the donor. Counselled amniocentesis in the three remaining patients led to the detection of an additional translocation carrier fetus. All four pregnancies resulted in live births. Fluorescence in-situ hybridization was applied to identify normal, balanced or imbalanced sperm cells of the donor. Accordingly, routine karyotype analysis of sperm donors was introduced, and is now recommended in the authors' unit.     

Can donor insemination be optimised?

OBJECTIVE: To compare the different donor insemination technics. MATERIAL AND METHOD: Analysis of the published studies about donor insemination which value the effectiveness of Intra Cervical Insemination (ICID) and Intra Uterine Insemination (IUID), the interest of ovulation induction, the possible complications, and the cost-effectiveness ratio. RESULTS: The meta-analysis of the Cochrane data base (10 comparative studies IUID versus ICID, 2568 donor insemination cycles) lead to a pregnancy rate per cycle (PRC) 17.77% with IUID versus 7.68% with ICID. The odds ratio is 2.63 (CI from 1.85 to 3.73). With these PRC, the direct cost per evolutive pregnancy is 54,780 F with ICID and 25,675 F with IUID. CONCLUSION: If it is possible to propose ICID to patient with an excellent regularity of ovulation. IUID with ovulation induction by gonadotropins is today the gold standard, and more especially as the law restrict the number of donor inseminations. Indeed, the IUID is two or three times more effective than ICID, consume the half of sperm straws, use a semen of moderate quality, there is no complication provided that the cycle is cancelled if there is more than two mature follicles and the cost-effectiveness ratio is greatly in favour with IUID.     

Open-identity donor insemination in the United States: is it on the rise?

Information about US donor insemination programs was reviewed to determine whether an increasing number are offering open-identity donation. Results indicate that indeed, numbers are rising and that the ratio of open-identity to anonymous sperm donors in a program increases the longer that the program has offered an open-identity option.     

Should requests for donor insemination on social grounds be expanded to transsexuals?

Donor insemination may provide an answer to transsexuals with female partners who have a wish for a child. Although the follow-up on children born in the context of these families is non-existent and the follow-up on transsexuals after sex reassignment surgery (SRS) is limited, fertility centres might consider accepting the requests of transsexuals with a female partner. Between 1997 and 2001, nine couples presented themselves at the Centre for Reproductive Medicine of the Dutch-speaking Brussels Free University, of whom five couples were accepted. Nevertheless, some caution is called for because transsexualism is socially not accepted. Moreover, transsexualism is still considered to be psychiatric condition. The following recommendations should be taken in consideration. Treatment should be limited to female-to-male transsexuals with a female partner. A multidisciplinary team of specialists should carry out the diagnosis for gender identity. Developmental problems of the gender-disordered child might interfere with socio-economic, psychological and emotional stability in adulthood. The period of sex reassignment should be nearly completed.     

Is hysteroscopic correction of an incomplete uterine septum justified prior to IVF?

This retrospective study examined the effect of hysteroscopic correction of an incomplete uterine septum on IVF outcome. Measurement of the Fm (fundal myometrial thickness) and Cm (cornual myometrial thickness) was performed by sonohysterography. Group 1 included patients diagnosed with incomplete septum (n = 119), fulfilling the two criteria of Fm >11 mm and Fm-Cm >5 mm, who underwent hysteroscopic incision of the incomplete septum. Group 2 consisted of 116 age-matched control patients with a normal uterine cavity who underwent IVF within the same time period. Main outcome measures were clinical pregnancy and spontaneous abortion rates. Patients in group 1 had a history of more spontaneous abortions than patients in group 2 (14.20 versus 6.03%, P = 0.04) as well as higher previous IVF failure (32.7 versus 20.6%, P = 0.04). After surgical correction of the septum in group 1, IVF pregnancy outcome was similar in both groups (clinical pregnancy and pregnancy loss of 47.80 versus 46.50% and 10.52 versus 20.3% respectively). A similar pregnancy outcome was found after the incision of the incomplete septum compared with a group with normal uterine cavity. Larger prospective and randomized controlled studies are needed to prove the positive effect of correction of an incomplete uterine septum on IVF outcome.     

Is letrozole superior to clomiphene for ovarian stimulation prior to intrauterine insemination?

Objective

To compare the efficacy of letrozole with clomiphene citrate for ovarian stimulation prior to intrauterine insemination.

Methods

A total of 272 patients underwent 362 cycles of stimulation prior to IUI from January 2009 to May 2011. One hundred and twenty-six patients (170 cycles) received letrozole 5 mg and 146 patients (192 cycles) received clomiphene citrate 100 mg for 5 days starting on day 3 of the cycle. Intrauterine insemination was done 36 ± 4 h after hCG injection in 99 patients (131 cycles) in the letrozole group and 115 patients (136 cycles) in the clomiphene group. The number of mature follicles and serum E2 levels was monitored on the day of hCG. Endometrial thickness was noted on the day of hCG and IUI as well. The pregnancy rate, the miscarriage rate, and other parameters were evaluated only for patients who underwent IUI.

Results

The mean number of mature follicles was significantly more in the clomiphene group (1.66 ± 1.69 vs. 1.41 ± 1.53) than in the letrozole group. No significant difference in endometrial thickness on the day of hCG administration was found; however, endometrial thickness was statistically significantly higher in the clomiphene group on the day of IUI (9.28 ± 1.43 vs. 8.77 ± 1.34). Serum E₂ levels on the day of hCG were statistically significantly higher in the clomiphene group (501.09 ± 2.45 vs. 214.79 ± 2.43 pg/ml). Pregnancy rate was 9.2 %/cycle and 12.12 %/patient in the letrozole group, and 8.1 %/cycle and 9.5 %/cycle in the clomiphene group; these differences were not statistically significant.

Conclusion

This study found no superiority of letrozole over clomiphene when used for ovarian stimulation and IUI.     

Does the timing of mock embryo transfer trial improve implantation in intracytoplasmic sperm injection cycles?

Aim.?To determine if endometrial trauma during embryo transfer trials (ETTs) improves implantation and clinical pregnancy rates in intracytoplasmic sperm injection treatment cycles.

Patients.?One-hundred fifty women undergoing their first IVF treatment were included in a prospective randomised study in a University hospital clinic. ETTs were performed either on day 21 of the previous cycle, or on day 6 of the controlled ovarian hyperstimulatin (COH) cycle, or conducted at least two cycles before COH cycle. Clinical pregnancy and implantation rates were compared between the groups.

Results.?There was no difference between the groups in terms of clinical pregnancy or implantation rates.

Conclusion.?Endometrial trauma by ETTs performed either during the preceeding cycle or on day 6 of the COH cycle does not improve pregnancy rates.     

Why search for a sperm donor online? The experiences of women searching for and contacting sperm donors on the internet

Whilst studies have examined the experiences of women who use clinic donors, to date there has been limited research investigating women’s motivations and experiences of searching for a sperm donor online. A total of 429 women looking for a sperm donor on Pride Angel (a website that facilitates contact between donors and recipients) completed an online survey. Fifty-eight percent (249) saw advantages of obtaining donated sperm online with the most common advantage reported as being able to connect with and meet the donor (n?=?50 (24%)). A third (n?=?157 (37%)) of the participants gave disadvantages, the most common reported was encountering ‘dishonest donors’ (n?=?63 (40%)). Most recipients (n?=?181 (61%)) wanted the donor to be ‘just a donor’ (i.e. to provide sperm and have no further contact). Whilst it was important for recipients to know the identity of the donor, some did not see this as important for the child and thus the level of information that parents have about the donor, and that which the child has, can differ. Finding a donor online blurs the distinction between categories of ‘anonymous’, ‘known’ and ‘identity release’ donations. Whilst the survey had a large sample size, the representativeness of the sample is not known.     

Is measurement of progesterone level prior to FSH stimulation useful in GnRH-antagonist cycles?

Aim. To reduce patient inconvenience during in vitro fertilization (IVF) cycles, some protocols delay intensive monitoring until mid-follicular stimulation. Others assess hormone levels prior to follicle-stimulating hormone (FSH) administration, not commencing stimulation until baseline progesterone (P4) levels (< 5 nmol/l) are achieved. Higher P4 levels (> 4.8 nmol/L) on the day of FSH trigger have been implicated in poorer pregnancy rates. This study evaluates the association of P4 levels at day 1–2 in gonadotrophin-releasing hormone (GnRH)-antagonist cycles with pre-trigger P4 levels and clinical pregnancy rates (CPRs). Method. All fresh GnRH-antagonist IVF cycles between June 2011 and June 2012, in which pre-FSH P4 levels were not routinely performed (group 1), were retrieved from the IVF Australia database and compared with controls (group 2). Results. There were 163 cycles in each group. P4 levels on the day of trigger were significantly higher in group 1 (3.75 vs. 2.77, p < 0.05). The incidence of pre-trigger P4 levels >4.8 nmol/l was significantly higher in group 1 (30 vs. 16, p < 0.05). The number of oocytes retrieved was higher in group 1 (11.1 vs. 9, p < 0.05), however fertilization rates were significantly lower in that group (53.6% vs. 61.2%, p < 0.05); CPRs were similar between the two groups (27.8% vs. 31.8%, p = ns). Overall, pregnancy rates were lower in cycles with pre-trigger P4 level of > 4.8 nmol/L compared with those with lower levels (15% vs. 32.5%, p < 0.05). Conclusion. We found that measurement of P4 level at early follicular phase was associated with significantly lower pre-trigger levels. However, this did not translate into a difference in CPR between the monitored and unmonitored groups. We have confirmed that elevation in pre-trigger P4 level is associated with halving of the CPR, indicating that the most important P4 measurements are those in the late follicular/pre-trigger phase.     

Is intracytoplasmic sperm injection safe?

OBJECTIVE: To review the pregnancy and birth outcomes of patients undergoing intracytoplasmic sperm injection (ICSI). DESIGN: Selective review of the literature. SETTING: Couples undergoing either conventional IVF or ICSI and their resulting offspring. PATIENT(S): None. MAIN OUTCOME MEASURE(S): None. INTERVENTION(S): None. RESULTS: These observational studies are unfortunately inherently biased. Regardless, the information and experiences from these large centers cannot be ignored. These experiences reveal that birth weight may be decreased by an amount that is generally not clinically relevant. Chromosomal and genetic abnormalities are increased probably only as a direct corollary to the underlying parental risk. Congenital malformations reveal no clustering of any single specific abnormality. Developmental assessment is available for up to 2 years, and no major delays have been identified in either motor or mental function. CONCLUSION(S): Intracytoplasmic sperm injection appears to be a safe alternative for couples who otherwise would be unable to achieve pregnancy. The inherent risks associated with these genetically "at risk" couples mandate thorough evaluation and counseling before undertaking ICSI.     

Is early initiation of infertility treatment justified in women over the age of 35 years?

Research questionNatural fecundity and the success of IVF and intracytoplasmic sperm injection (ICSI) rate both decrease with age. For this reason, in women older than 35 years, it is generally recommended to start the infertility work-up after only 6 months. This assumption, however, may expose couples to over-diagnosis and over-treatment.DesignA theoretical model aimed at assessing the effects of starting the infertility work-up after 6 rather than 12 months of trying to conceive naturally was developed. The assumptions of the model were as follows: infertile women are treated with IVF/ICSI for up to three cycles; IVF/ICSI success rate at first cycle linearly declines with age (3% per year between the ages of 35 and 45 years); the drop-out rate after the first and second cycle is 18% and 25%, respectively; the relative reduction of the success rate at second and third cycle is 16% and 26%, respectively.ResultsEarly initiation of treatment moderately improved the cumulative chances of live birth resulting from a full IVF/ICSI programme. This improvement is dependent on age. Specifically, it increased from 2.0% at age 35 years to 3.0% at age 43 years. Conversely, the incremental success rate per single IVF cycle was mainly stable, varying only from 1.4% at age 35 years to 1.3% at age 43 years.ConclusionsIn women older than 35 years, early initiation of the infertility work-up is associated with only a modest increase in the rate of success of IVF/ICSI. In most scenarios, this advantage may compare unfavourably with the chances of natural conception during the 6-month period.     

Measurement of serum estradiol/progesterone ratio on the day of embryo transfer to predict clinical pregnancies in intracytoplasmic sperm injection (ICSI) cycles. Is this of real clinical value?

Study objectiveTo assess the value of measuring serum estradiol/progesterone (E₂/P) ratio on the day of embryo transfer (ET) in intracytoplasmic sperm injection (ICSI) cycles to predict clinical pregnancies.DesignA prospective study.SettingThe assisted reproduction unit of a large University Maternity Hospital.Materials and methodsFifty seven women consecutively treated by ICSI for male factor infertility were included in the study. Early luteal serum E₂ and P were measured on the day of ET and serum E₂/P ratios were calculated for clinical pregnancies and non-clinical pregnancy cycles.Main outcome measureClinical pregnancy rate.ResultsThirty four women failed to have clinical pregnancy (Non-clinical pregnancy group) while 23 women had clinical pregnancies (Clinical pregnancy group). There were no statistically significant differences between the two outcome groups regarding the median values for E₂ levels, P levels and E₂/P ratios (655 pmol/l, 172.5 nmol/l and 2.8 for non-clinical pregnancy cycles versus 814 pmol/l, 180 nmol/l and 2.9 for clinical pregnancy cycles, respectively). Receiver-operating characteristic (ROC) curve for E₂/P ratio was constructed to predict clinical pregnancies, the area under the curve (AUC) was 0.513 (95% confidence interval, 0.377–0.648; P, 0.865) and the best cut-off value was an E₂/P ratio of 2.5 (sensitivity of 69.57%, specificity of 44.12%, positive predictive value of 45.7% and negative predictive value of 68.2%).Major conclusionsMeasurement of E₂/P ratio on the day of embryo transfer in ICSI cycles is not of clinical value to predict clinical pregnancies.