Patients' attitudes towards donation of surplus cryopreserved embryos for treatment or research

BACKGROUND: The aim of the study was 2-fold: first, to investigate couples' reasons for not using cryopreserved embryos within the maximum storage period; second, to study their attitudes towards potential embryo donation for specific purposes. METHODS: A questionnaire was sent to 284 IVF/ICSI couples who experienced destruction of their cryopreserved embryos (n=1180) because the cryopreservation period exceeded the Danish legislative limit of 24 months. RESULTS: Seventy-four per cent of the couples responded. The main reasons for not utilizing surplus embryos was 'successful delivery' (85%), 'consider family completed' (61%) and 'too short legislative limit for cryopreservation' (59%). Sixty per cent of the couples agreed to the concept of donation of cryopreserved embryos for infertility research, 57% responded affirmatively to donation for stem cell research and 49% for stem cell treatment, but only 29% agreed to the concept of donation to infertile couples. Multiple logistic regression analysis showed that delivery of a child after IVF treatment (OR 3.8, 95% CI 1.4-10.2) and female age <35 years (OR 2.2, 95% CI 1.3-6.0) were predictive of agreement to the idea of donation for stem cell research and stem cell treatment respectively; however, male age, duration of infertility, mode of conception (IVF or ICSI) and having IVF children were not significant predictors. The following predictive variables were entered into the analysis: female and male age, duration of infertility, IVF versus ICSI, donor semen and +/- IVF children. CONCLUSIONS: This study shows that 23% of all couples having cryopreserved embryos do not utilize them for further treatment within the legislative storage period of 2 years. A major reason is successful delivery. More than half of these patients agreed to the concept of donation of surplus outdated embryos for research, whereas less than one-third agreed to donation to other infertile couples. Based on these figures, an alternative utilization of surplus embryos for stem cell research would require a 100-fold larger pool of available embryos to provide a realistic basis for this purpose.     

The diagnosis of male infertility--prospective time-specific study of conception rates related to seminal analysis and post-coital sperm--mucus penetration and survival in otherwise unexplained infertility

Infertile women without any inherent female infertility factorsand able to secrete normal cervical mucus were studied prospectivelyin relation to post-coital sperm—mucus penetration (PCT)and their partner's seminal analysis, excluding men with azoospermia.Time-specific cumulative conception rates calculated as forlife-table analysis were related to each measured seminal variableon routine analysis of 2–3 samples (volume, density, proportionwith progressive motility, and proportion with normal morphology);to various derivatives from combinations of these variables;to seminal findings after vital staining; and to the PCT results.The best seminal predictor of fertility was the motile normalsperm density (MNSD), the 18 month conception rates being 57.4%+ 4.6 (SE) and 30.2% + 5.9 (ratio 1.9, P < 0.001) above andbelow a derived threshold value of 4 x 10⁶/ml. The PCT led torates of 55.6% ± 4.3 and 14.9% ± 5.1 (ratio 3.73,P < 0.001) for positive and negative results, respectively.The PCT also gave rise to a significantly distinct intermediatepoor-psitive sub-group (conception rate 30.6% ± 9.0).Seminal analysis (the MNSD) did not affect the conception rateassociated with a positive PCT but helped to discriminate furtherwith a negative PCT (conception rates 22.5% ± 8.7 withan MNSD above 4 x 10⁶/ml versus 5.6% ± 4.8 below, P <0.05). The PCT was the single best predictor of fertility butseminal analysis (the MNSD) was of additional value after anegative PCT.     

Improvement of cervical mucus viscoelasticity and sperm penetration with sodium bicarbonate douching

The aim of the study was to evaluate the influence of vaginal douching with sodium bicarbonate (NaHCO3) upon cervical mucus viscoelasticity and sperm penetration in vitro and in vivo. Twenty-five couples with primary infertility for greater than 12 months participated in the study. The selection criteria were: (i) semen quality compatible with conception, (ii) regular ovulatory cycles and (iii) repeated negative post-coital test (PCT). After at least one inventory cycle, three consecutive cycles were studied. In the second and third cycles, vaginal douching was performed with either 1.5% (w/v) NaHCO3 or 0.9% (w/v) NaCl (randomized procedure). The viscoelasticity of the cervical mucus, sperm penetration tests (SPT) and PCTs were analysed. The viscoelasticity of mucus samples after NaHCO3 douching was significantly lower than the viscosity after NaCl douching (P less than 0.001, n = 16) and in the control cycles (P = 0.003). The SPT scores were significantly higher in the NaHCO3 cycles than in the NaCl cycles (P = 0.004, n = 22) and in the control cycles (P less than 0.001). The PCT scores proved to be significantly higher after NaHCO3 douching than after NaCl douching (P = 0.002, n = 21). Comparison of NaHCO3 and control cycles also showed a significant improvement of the PCT score after NaHCO3 douching (P less than 0.001).     

Differences in time to natural conception between women with unexplained infertility and infertile women with minor endometriosis

BACKGROUND: Opinion remains divided as to whether finding endometriotic lesions in the absence of adhesions has an adverse effect on the likelihood of conception. METHODS: This was a retrospective study of 192 fully investigated infertile couples, followed up for up to 3 years following laparoscopy. Women studied were ovulating, <40 old years and their partners had normal sperm parameters. All 117 women with unexplained infertility and 75 with minimal/mild endometriosis without adhesive disease were managed conservatively. RESULTS: Women with endometriosis were found to have a lower probability of pregnancy compared with women with unexplained infertility (36% versus 55%; P<0.05). Other factors adversely associated with pregnancy were primary infertility, smoking and longer duration (>3 years) of infertility. However, the effects of duration of infertility and primary infertility were not observed to be statistically significant for women with endometriosis. CONCLUSIONS: The findings, although undertaken in a select population undergoing laparoscopy, suggest the likelihood of pregnancy is reduced in infertile women with minimal/mild endometriosis compared with those infertile women with a normal pelvis. Duration of infertility and a previous history of pregnancy are important in predicting the likelihood of pregnancy in women with no obvious cause for their infertility (unexplained), whilst the relationship may be more complex in women with minor endometriosis     

Infertility, infertility treatment and twinning: the Danish National Birth Cohort

BACKGROUND: We have previously observed that an increasing time to pregnancy (TTP) is associated with a reduced frequency of twin deliveries in couples not receiving infertility treatment. By using updated information, we assessed the frequencies of dizygotic (DZ) and monozygotic (MZ) twin deliveries as a function of infertility (TTP > 12 months), as well as infertility treatment. METHODS: From the Danish National Birth Cohort (1997-2003), we identified 51 730 fertile couples with TTP 12 months and 5163 infertile couples who conceived after treatment. Information on zygosity, available for part of the cohort (1997-2000), was based on standardized questions on the similarities between the twins at the age of 3-5 years. RESULTS: Compared with fertile couples, the frequency of DZ twin deliveries was lower for infertile couples conceiving naturally (odds ratio 0.4, 95% confidence interval 0.2-0.7) and was much higher for infertile couples conceiving after treatment (17.3, 14.4-20.7). The frequency of DZ twin deliveries decreased with TTP in untreated couples, whereas the frequency of MZ twin deliveries remained constant. CONCLUSIONS: The frequency of DZ twin deliveries decreased with TTP and substantially increased with infertility treatment, whereas MZ twin deliveries remained substantially unchanged.     

Definition and prevalence of subfertility and infertility

A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.     

Embryo donation: outcome and attitudes among embryo donors and recipients

The outcome of an embryo donation programme was evaluated and attitudes among donors and recipients studied by means of a questionnaire survey. A total of 27 couples went through 54 treatment cycles with frozen-thawed embryos donated by other infertile couples. The indications for treatment were premature or incipient ovarian failure in combination with severe male factor infertility. The mean age of the recipient women was 36 years, and that of the recipient men was 35 years. The mean duration of infertility was 8 years (range 2-19 years). Forty-six couples donated 209 excess frozen embryos to the programme. The clinical pregnancy rate in the recipients was 27.8% (15/54) per embryo transfer. An average of 1.9 embryos were transferred on each occasion. The response rate to the questionnaire was high (80-91%). Significantly more recipients (69%) than donors (47%) considered that the child should be informed about the manner of conception (P < 0.05). Some 29% of recipients and 42% of donors thought that the child should receive identifying information concerning the donor couple. The interest of the offspring, not only as regards knowing his/her genetic origin but also knowing full-blood genetic siblings, should be kept in mind in embryo donation programmes.     

Risk factors for female and male infertility: results of a case-control study.

In order to evaluate male and female risk factors for infertility in a case-control study, we have compared all couples in a French administrative region consulting for primary or secondary infertility (of more than one year's duration) with couples in which the woman had given birth during the year of the study. For any one couple, a history of varicocele, male genital infections or testis damage multiplies the risk of primary infertility by a factor of 28, 3 and 4 respectively, and previous female infections (salpingitis) multiply the risk by 45. Similarly, a history of ectopic pregnancy, sexually transmitted diseases or salpingitis multiplies the risk of secondary infertility by a factor of 5, 4 and 7 respectively, and a history of varicocele multiplies this risk by 4.     

The Frequency of Antisperm Antibodies in the Cervical Mucus of Women With Poor Postcoital Tests and Their Effect on Pregnancy Rates

PROBLEM: To determine the impact of the presence of antisperm antibodies (ASAs) in the cervical mucus of female partners in couples with unexplained poor postcoital tests (PCT). Furthermore, the efficacy of intrauterine insemination (IUI) in these same patients was determined by pregnancy rates (PRs). METHOD: Pregnancy rates following IUI in patients with infertility and poor postcoital tests, whether the cervical mucus was positive or negative for ASAs, were evaluated. RESULTS: The 6-month PRs were similar in the ASA negative (40.5%) versus the positive (42.4%) group. CONCLUSIONS: It appears that the antifertility effect of ASA may be mainly the immobilization of sperm in the cervical mucus, and thus, performing IUI may effectively correct the problem.     

Infertility: Infertility evaluation in fertile women: a model for assessing the efficacy of infertility testing

A standard infertility evaluation consists of a semen analysis,hysterosalpingogram, post-coital test, endometrial biopsy andlaparoscopy. Although these tests are well grounded in clinicalexperience, information on their ability to discriminate betweenfertile and infertile couples is limited. In this study, weperformed standard infertility tests plus two others-sperm antibodiesand cervical culture for Mycoplasma hominis and Ureaplasma urealyticum–onfertile and infertile couples. Women in the fertile group wereselected from those who had delivered a child within the previous2 years and who were scheduled for a laparoscopic tubal ligation.Women in the infertile group were selected from those presentingfor an infertility evaluation (mean duration of infertility4.2 years), and they were matched by age (±3 years) andrace with fertile subjects. Subjects were recruited from bothprivate and clinic patients. A total of 64 couples (32 matchedpairs) completed the evaluation. At least one ’abnormal‘infertility test was found in 69% of fertile and 84% of infertilecouples. With the exception of tubal damage and endometriosis,which as expected were more common in infertile couples, nosignificant differences between groups for remaining infertilityfactors could be demonstrated. Despite the small size of thecurrent study, these results confirm the feasibility and importanceof comparisons of the prevalence of infertility factors in fertileand infertile couples.     

Investigation of the infertile couple: a basic fertility work-up performed within 12 months of trying to conceive generates costs and complications for no particular benefit

The current approach of the basic fertility work-up has been questioned recently in this journal. Based on new data on human fecundity, the authors advocated starting the fertility work-up after just 6 months of trying to conceive instead of the usual 12 months. In women younger than 39 years and with a regular cycle, there are several arguments why the basic fertility work-up should not be done earlier than after 12 months of child wish. Firstly, 50% of couples who have tried to conceive for 6 months without success will conceive in the next 6 months without any treatment. Secondly, the prevalence of fertility diseases is lower in couples who have been trying to conceive for 6 months as compared with those who have been trying for 12 months. Performance of a fertility work-up at this stage will lead to an increase in false-positive diagnoses compared with performing them at 12 months of subfertility. Thirdly, fertility treatment will have fewer additional effects in couples with good spontaneous conception prospects (6-12 months child wish), compared with subfertile couples who have poor prospects. At present, none of the available fertility treatments have success rates comparable with no intervention in these women, and postponement of treatment in such couples will prevent complications such as ovarian hyperstimulation syndrome and multiple pregnancies. We argue that the fertility work-up should not be offered to couples with a duration of child wish of <12 months, except for women with ovulation disorders and women of 39 years and older.     

Male infertility risk factors in a French military population

We investigated infertility risk factors by conducting a population-based case-control study in the military population of the French town of Brest. Sixty couples who had sought medical advice for infertility of more than 12 months duration (cases) were compared with 165 couples who had had a child (controls). All the men in these couples had been employed by the military. The infertility risk factors studied were male and female medical factors, occupational and environmental exposures. We obtained age-adjusted odds ratios of 7.4 [95% confidence interval (CI): 1.4--39.5] for testis surgery, and 13.0 for varicocele (95% CI: 1.4--120.3) in men. In logistic regression, the age-adjusted odds ratio for men who had worked in a nuclear submarine was found to be 2.0 (95% CI: 1.0--3.7), and that for heat exposure was 4.5 (95% CI: 1.9--10.6). One limitation of this study is the lack of exposure measurements, especially for potential exposure to nuclear radiation (type of reactor used in nuclear-powered submarines, inability to obtain personal dosimeters worn by military personnel working in nuclear submarines). In conclusion, this study suggests that in this military population, having worked as a submariner in a nuclear-powered submarine, and having worked in very hot conditions, should be considered as risk factors for infertility.     

Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study

BACKGROUND: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. METHODS: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. RESULTS: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. CONCLUSIONS: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.     

Prognostic factors in assessment and management of male infertility.

Evaluation of 304 infertile couples with at least one abnormal semen analysis (sperm density < 20 x 10(6)/ml and/or motility < 50%) and no apparent female factors was performed in a multicentre prospective cohort study. In 73 cases therapeutic donor insemination was performed (TDI group) with a resulting pregnancy rate of 48%. The remaining 231 couples (non-TDI group) had an overall pregnancy rate of 25%. The TDI group had a shorter duration of infertility. The ages of both partners were comparable in TDI and non-TDI groups. In the non-TDI group, univariate analysis resulted in identification of six clinical variables associated with a change in pregnancy rates. The strongest association was noted for length of infertility. There was a weaker association for semen volume, concentration of leukocytes in semen, history of pregnancy in the female partner and laparoscopy. Multiple variable analysis of data from the non-TDI group revealed that independent predictors of pregnancy were 'duration of infertility' and 'history of pregnancy in the female partner'. The multiple variable modelling suggested that (i) an increase in the length of infertility by 1 month prolongs the time to pregnancy by an additional 1.6% (95% confidence interval: 1.5-1.7%); and (ii) a history of past pregnancy in the female partner reduces the time of pregnancy by 51% (95% confidence interval: 47-56%).     

The sperm-mucus interface: patterns of disorder in the diagnosis of specific causes of penetration failure causing infertility

In 94 infertile couples with negative postcoital tests (PCTs) the results of an in-vitro sperm-mucus invasion test (SMIT) were compared with seminal analysis (excluding sperm density less than 1 x 10(6)/ml) and agglutination assays for antisperm antibodies in semen (MAR, TAT) and in mucus (TAT). Abnormalities at the sperm-mucus interface were classed into three types. (i) Failure to form semen clefts and of spermatozoa to colonize the clefts was closely correlated with oligo-asthenoteratozoospermia, and vice versa, the two tests agreeing in 90% of cases (P less than 0.001). Most of the discrepancies, in which sperm-dense clefts developed despite low sperm counts, were due to antisperm antibodies in semen. (ii) Failure of spermatozoa to invade mucus, despite normal sperm colonization of clefts, was closely correlated with the presence of antisperm antibodies in semen (positive MAR or TAT), and vice versa, the tests agreeing in 81% of cases (P less than 0.001). (iii) Failure of sperm survival after normal invasion of mucus could not be correlated significantly with the TAT results on mucus, but more extensive study of this question is needed. Finally a normal SMIT result was associated with a significantly improved chance of conception (39 versus 10% at 12 months), particularly with artificial insemination, suggesting undisclosed coital failure as the cause of the negative PCT. In conclusion, the invasion test, when assessed in the foregoing detail, offers a reliable and simple substitute for laboratory assessment of both seminal quality and the presence of antisperm antibodies in semen, and would be applicable in general infertility practice everywhere.     

International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care

INTRODUCTION The purpose of the present study was to review existing population surveys on the prevalence of infertility and proportion of couples seeking medical help for fertility problems. METHODS Population surveys, reporting the prevalence of infertility and proportion of couples seeking help in more and less developed countries, were reviewed. RESULTS Estimates on the prevalence of infertility came from 25 population surveys sampling 172 413 women. The 12-month prevalence rate ranged from 3.5% to 16.7% in more developed nations and from 6.9% to 9.3% in less-developed nations, with an estimated overall median prevalence of 9%. In 17 studies sampling 6410 women, the proportion of couples seeking medial care was, on average, 56.1% (range 42-76.3%) in more developed countries and 51.2% (range 27-74.1%) in less developed countries. The proportion of people actually receiving care was substantially less, 22.4%. Based on these estimates and on the current world population, 72.4 million women are currently infertile; of these, 40.5 million are currently seeking infertility medical care. CONCLUSIONS The current evidence indicates a 9% prevalence of infertility (of 12 months) with 56% of couples seeking medical care. These estimates are lower than those typically cited and are remarkably similar between more and less developed countries.     

Epilepsy and febrile seizures in children of treated and untreated subfertile couples

BACKGROUND: Only few studies have addressed the long-term neurological outcomes of children born by subfertile couples. We studied the risk of epilepsy and febrile seizures in children of treated and untreated subfertile couples. METHODS: The study included 83 194 live singletons born by mothers who took part in the Danish National Birth Cohort (DNBC). Information on time to pregnancy (TTP) and infertility treatment was reported by the mothers in computer-assisted telephone interviews. Data on epilepsy and febrile seizures were extracted from the Danish National Hospital Register. RESULTS: Overall, children of subfertile couples (TTP > 12 months) had a 51% higher risk of epilepsy [incidence rate ratio (IRR): 1.51; 95% confidence interval (95% CI): 1.17-1.94] compared with children of couples with a TTP of 0-5 months. The corresponding estimates were 1.71 (95% CI: 1.21-2.42) if the couples had received infertility treatment and 1.38 (95% CI: 1.00-1.89) if they conceived spontaneously. Children of subfertile couples did not have a higher risk of febrile seizures except for those who received hormonal treatment (HT) with or without intrauterine insemination (IRR = 1.37; 95% CI: 1.14-1.66). CONCLUSIONS: Children of subfertile couples had a slightly increased risk of epilepsy, and the risk tended to be higher for children of couples who received infertility treatment. Whether this reflects side effects of treatment or severity of subfecundity is not known.     

The risk of infertility among hairdressers. Five-year follow-up of female hairdressers in a Danish national registry

BACKGROUND: One in seven married couples is involuntarily infertile. Several chemical exposures in the work environment have been hypothesized to affect female reproduction, and some are present in products used in hairdressing and related trades. Recent Swedish findings indicate that employment in hairdressing poses a risk for female reproductive function. This study examined the possible association between work as a hairdresser and subsequent hospital contact due to female infertility. METHODS: A cohort of all women in Denmark aged 20-44 years on 1 January 1998 (baseline) and registered as economically active hairdressers, according to national registers, was formed to calculate age-standardized risk ratios (RRs) for hospital contacts due to female infertility during a 5-year follow-up period. Hairdressers were compared to a standard population, that is, all economically active women in Denmark aged 20-44 years at baseline, and to women working as shop assistants. RESULTS: Sixty-eight cases of hospital contact due to female infertility were observed among the female hairdressers. On the basis of the standard population, the expected number was 73.27, which gives an observed RR of 0.928 (95% CI: 0.72-1.18). Hairdressers and shop assistants exhibited similar rates of hospital contact due to female infertility (1.01; 95% CI: 0.77-1.29). CONCLUSION: The findings are not corroborating the hypothesis that hairdressers are at increased risk of infertility, but small risks in the entire group or high risks in small subgroups may not be detected by the study.     

Possibilities and limitations of techniques of assisted reproduction for the treatment of male infertility

Since relatively few spermatozoa are needed for oocyte fertilization during gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF), these methods have been applied in couples with infertility due to male causes. Forty-six couples with male factor infertility were enrolled in this study and results were compared with those attained in 48 couples treated with the same techniques for other than male causes. Overall, GIFT resulted in 26% ongoing pregnancies. GIFT seems to be particularly successful when the sperm concentration is 20 x 10(6)/ml or more, but sperm motility and/or morphology are poor. Nine pregnancies occurred out of 26 GIFT cycles in 18 cases selected on this basis. The ongoing pregnancy rate after IVF was 16% per patient. The latter treatment should be attempted in male immune infertility and in cases with a low sperm concentration, with or without abnormal sperm motility and/or morphology. In these circumstances, five pregnancies were attained out of 28 cycles in 14 cases. For similar sperm concentrations, the conception rate per cycle attained with techniques of assisted reproduction was more than twice that attained with conventional treatment of male infertility.