Artificial procreation with frozen donor semen: experience of the French Federation CECOS

The French Federation CECOS (Centre d'Etude et de Conservation du Sperme Humain) sperm banks collate the results of its 20 centres and provides annual reports on their activity. Since its creation in 1973, approximately 17,000 pregnancies have been obtained using frozen donor semen either for artificial insemination by donor (AID) or for in-vitro fertilization. The recruitment of the donors was very strict, only 62% of the 6810 donor candidates were accepted. The overall mean success rate per cycle for all women who began AID was approximately 8%, and the theoretical cumulative success rate was 48% at six cycles and 66% at 12 cycles. The population of recipient patients was very heterogeneous, including fertile, sub-fertile and infertile women. Some of these female factors have been analysed.     

Cohort follow-up of couples with primary infertility in an ART programme using frozen donor semen

BACKGROUND: This study was designed to determine the crude cumulative live-birth rates in a cohort initiating frozen donor semen treatment until completion. METHODS: This cohort study included 588 couples with primary infertility in one University Hospital centre. The treatment sequence involved first artificial insemination (AID) followed by IVF if necessary (IVF-D). Live birth, drop-out for personal or medical reasons and recourse to IVF-D were recorded for all patients. Live births and drop-out were expressed both as rates per cycle and crude cumulative rates. RESULTS: At the completion of AID and IVF-D cycles, 406 couples in the cohort (69%) achieved a live-birth and 182 couples (31%) discontinued treatment. In most cases, couples stopped treatment for personal reasons (74%) whereas fewer couples were denied further treatment for medical reasons (26%). CONCLUSIONS: This is the first report on the crude cumulative live-birth rate in a cohort after AID and IVF-D cycles. Although calculation based on crude cumulative live-birth rate shows lower results in comparison with life table analysis, this method allows patients to obtain an insight into their actual chances of achieving a successful pregnancy.     

Achievement of second parenthood in an ART programme using frozen donor semen: cohort follow-up

BACKGROUND: This study was designed to determine the efficacy of a programme using frozen donor semen in a cohort of patients returning for treatment after previously conceiving through donor insemination (DI). METHODS: The cohort included 222 couples with secondary infertility (previous live birth) in one University Hospital Centre. The treatment sequence involved DI cycles until completion. Live births, drop-out for personal or medical reasons and recourse to IVF with donor semen (IVF-D) were recorded for all patients. Live births were expressed as both rate per cycle and crude cumulative rate. RESULTS: At the end of the DI cycles, 65% of couples in the cohort achieved second parenthood. Most of them (77%) succeeded after only four DI cycles. The majority of couples who stopped treatment did so for personal reasons. CONCLUSIONS: Patients involved in a second parenthood project belong to a 'selected' population. Management and counselling of such patients need to reconcile the early efficacy of DI cycles, the invasiveness of the IVF-D procedure and the availability of donor semen.     

Andrology: The predictive value of computer-assisted semen analysis in the context of a donor insemination programme

In this paper we examine the value of both conventional andcomputer-assisted semen analysis (CASA) using the Hamilton-ThornHTM-S 2030 in predicting the in-vivo fertility of cryopreserveddonor semen. Semen samples were examined prospectively and dataon the conventional criteria of semen quality, sperm morphometryand movement were collected. Of 61 ejaculates identified, 33achieved pregnancies (‘successful’) and 28 failedto do so (‘unsuccessful’), despite inseminationinto at least four different normal female recipients. Whenthe post-thaw semen profiles were compared, no differences wereobserved between the two groups in respect of the conventionalcriteria of semen quality determined by conventional laboratorytechniques; however, there were differences in respect of bothmorphometry and movement characteristics determined by the HTM-S.When multiple logistic regression was used to examine the abilityof the variables measured to predict the achievement of pregnancy,the conventional criteria of semen quality were of no value(X² = 6.67, P = 0.353). However, the CASA assessment successfullypredicted outcome in 86.9% of cases (X² = 44.3, P = 0.0021).It was concluded that CASA assessment is of significant valuein predicting the ability of an ejaculate to achieve pregnancy.     

British Andrology Society guidelines for the screening of semen donors for donor insemination (1999)

The British Andrology Society (BAS) guidelines for the screeningof semen donors have undergone a recent review, and followingconsultation with members of the Society and with experts inthe allied professions, the following revised guidelines havebeen issued. Major changes include the introduction of an upperage limit for semen donors (<40 years old) and the generalexclusion of men who are seropositive for cytomegalovirus asdonors. The BAS recommends the screening of prospective semendonors for chromosomal abnormalities and for cystic fibrosiscarrier status. Following the report of cross-contaminationof human cells with hepatitis B virus within a liquid nitrogenstorage vessel, the BAS recommends that steps be taken to ensurethe safe cryopreservation of donor gametes.     

A comparative evaluation of intracervical and intrauterine routes in donor therapeutic insemination

The relative efficiency of intrauterine insemination with washedspermatozoa versus intracervical deposition of semen was examinedin donor insemination for therapeutic reasons. Fecundabilityin a group of 26 women who desired insemination as a treatmentfor azoospermia or severe astheno-oligozoospermia in their partnerwas comparable, despite the 10-fold higher numbers employedusing the intracervical route.     

Andrology: The screening for cytomegalovirus antibody in semen donors and recipients within a donor insemination programme

A total of 67 semen donors (62 Caucasian and five non-Caucasian)were tested for the presence of immunoglobulin G antibodiesto cytomegalovirus (CMV). Ten (16%) of the Caucasian donorstested positive for CMV, while four (80%) of the non-Caucasiandonors were positive. A total of 131 women receiving donor insemination(114 Caucasian and 17 non-Caucasian) were tested. Of these,43 (38%) of the Caucasian recipients tested positive for CMV,while 16 (94%) of the non–Caucasian recipients were positive.There was a significant association between the incidence ofpositive tests and the age of the Caucasian recipients.     

The relationship between fertility potential measurements on cryobanked semen and fecundity of sperm donors

Sperm penetration assay (SPA) scores obtained from cryobanked semen were correlated with therapeutic insemination (TI) fecundity in a group of established sperm donors, thereby evaluating the efficacy of the SPA in screening donors for sperm banking. While the SPA has been used to separate fertile from infertile males, we altered assay conditions to use frozen semen and to distinguish performance among fertile donors. Three frozen ejaculates from 11 pregnancy-proven donors were analysed. Of 905 TI cycles, 275 recipients achieved 95 pregnancies. There were no significant relationships between fecundity and donor semen, washed sperm parameters, sperm recoveries or recipient age. A significant relationship was revealed between mean SPA scores (range 8.7-66.6 penetrations/ovum) and donor fecundity (range 0.04-0.16, P < 0.03). Sperm concentration was varied in an effort to establish the most sensitive test condition. Using 0.25x10(6) motile spermatozoa/ml, a highly significant relationship was observed (P < 0.002). The four donors with the lowest SPA scores achieved the four lowest fecundities. It is concluded that a modified SPA can be used on frozen donor semen to estimate donor fertility potential. If applied routinely in donor semen banking, poor quality applicants could be excluded, thereby increasing pregnancy rates while decreasing donor screening costs.     

In-vitro fertilization with donor sperm after failure of artificial insemination

This retrospective study compares results of artificial inseminationby donor (AID) and in-vitro fertilization (IVF) trials, andespecially of IVF treatment with fresh donor spermatozoa inpatients who were unsuccessfully treated on 18 occasions byAID using frozen semen. AID gives cumulative pregnancy rateof 54.6% after six trials. But after 18 trials, 22.4% of thepatients were still not pregnant. Treating them with IVF gavea probability of pregnancy as good as in the other IVF patients,53.9% after six trials. However, pregnancy loss rates differedresulting in cumulative normal pregnancy rates of 16.2% in AIDcycles ranking from 19 to 24 compared with 41.8% when goingto IVF. In ‘ex-ATD’ women, significantly more follicleswere punctured, but the number of oocytes obtained and fertilized,embryos replaced, and the incidence of pregnancy did not differfrom the other patients. Considering separately the variousinfertility factors encountered in the patients, the pregnancyrates still did not differ between ex-AID women and the others.Changing from long-term failed AID to IVF is certainly acceptableand even more so with the newly introduced technique of trans-vaginalpuncture. The female infertility factors involved in AID failureare corrected in IVF.     

Gamete intra-fallopian transfer with cryopreserved donor semen following AID failure

Results are presented of gamete intra-Fallopian transfer with cryopreserved donor semen in cases of male infertility with azoospermia or extreme oligozoospermia. The female partners had no detectable infertility problems and they had first received 10 cycles of intracervical AID without success. Forty-one GIFT cycles performed on 22 such patients gave an overall pregnancy rate of 26.8% (11/41). In 64% (9/14) of these cases, pregnancy occurred after the first GIFT attempt. From these results it is suggested that GIFT with donor semen may be a reasonable alternative after AID failure. The probable reasons for success of GIFT are discussed.     

One-hundred-and-six gamete intra-fallopian transfer procedures with donor semen

A single attempt of gamete intra-Fallopian transfer was performed in 106 patients, who had previously failed to become pregnant after a certain number of artificial donor inseminations. A maximum of six unselected oocytes were transferred into the tubes. Fifty-five clinical pregnancies (51.9%) were obtained. There were 11 multiple pregnancies (20%) and 10 miscarriages (18.1%). Only one ectopic pregnancy occurred (1.8%). The age of the patients and the previous number of failed inseminations did not have any significant influence on the outcome of the procedure, whereas the number of transferred oocytes had a proportional, significant correlation with the pregnancy rate.     

Andrology: Preferences for intracytoplasmic sperm injection versus donor insemination in severe male factor infertility: a preliminary report

With the advent of intracytoplasmic sperm injection (ICSI),our programme noted a drop in the number of couples using donorinsemination (DI) for severe male factor infertility. Over thefirst 8 months in which our infertility programme offered bothtreatments, 27 consecutive couples scheduled for ICSI and 15consecutive couples scheduled for DI were evaluated Since allpatients in our infertility programme beginning in-vitro fertilization(TVF) with planned ICSI or starting DI undergo a semi-structuredpsychological interview, the psychologist's clinical notes aswell as the medical chart were reviewed and coded retrospectivelyto determine factors related to a couple's treatment choice.Couples who chose IVF-ICSI over DI had a higher occupationalstatus and included husbands with higher educational levels.Their most common motivation was to have the husband's biologicalchild (93% of couples in the ICSI group). The most common motivationfor choosing DI (60% of DI couples) was that IVF was not financiallyaffordable. Choice of treatment was not related to psychologicaladjustment, the husband having prior biological children, orhis risk of passing on a genetic defect to offspring. Thesepreliminary data raise the concern that, with the success ofICSI, DI may change in the USA from being an option dictatedby semen quality to a second choice treatment utilized for economicreasons.     

The use of intrauterine insemination in Australia and New Zealand

BACKGROUND: There is good evidence in the literature in favour of intrauterine insemination (IUI) as the most cost-effective treatment for unexplained and moderate male factor subfertility. However there is no published data on whether this evidence is being translated into clinical practice. METHODS: We identified fertility centres within Australia and New Zealand registered with the Reproductive Technology Accreditation Committee of the Fertility Society of Australasia. Thirty-seven of these units were then sent a postal survey to establish current clinical practice. RESULTS: Nearly a third of centres promote IVF as first-line treatment even in the presence of patent tubes and normal semen while, when semen parameters are reduced, IUI is rarely considered. One in five (20%) units remain unconvinced of the cost-effectiveness of IUI. When IUI is used, it is virtually always combined with ovarian stimulation with marginally more units using clomiphene citrate than gonadotrophins. CONCLUSIONS: Although it may take relatively more treatment cycles to achieve pregnancy, there are considerable advantages to the patient in terms of risk/benefit ratio and financial cost associated with IUI compared with IVF. In the current climate of evidence-based medicine, as clinicians we are obliged to translate this into our practice. It appears from our survey that in many units this is not happening.     

Attitudes towards donor insemination--a post-Warnock survey

In a multi-centred study, a total of 799 patients, donors andhealth-care professionals concerned with artificial inseminationwith donor semen (AID) responded to a questionnaire regardingtheir attitudes towards current provision of AID services andproposed legislation. There was little support for any fundamentalchange in the way in which AID is practised, at least in thosecentres. The anonymous status of the donor met with universalagreement. Although there was some support for the communicationof non-identifying details to the recipient couple, where theywanted them, there was no support for any legislation whichmight give the AID child a right of access to details of thedonor. The greatest divergence of opinion was over the questionof who should have access to AID treatment and whether or notscreening procedures should be applied to prospective parents.Most respondents felt that the closed and confidential relationshipbetween the clinic and the other parties involved should notautomatically be extended to general practitioners or any nationalbodies. In respect of specific recommendations of the WarnockCommittee, there was support for changes which might legitimizeor assist the present system, but not for any which might berestrictive.     

Methods to increase the success rate of artificial insemination with donor semen

Donor insemination was performed in two fertility clinics usingcryopreserved semen from the same sperm bank. Donors were selectedin agreement with American Fertility Society recommendations.In the first clinic, cup insemination was combined with intra-uterineinsemination in 321 cycles. Follicular development was closelymonitored with vaginal echography and serum hormonal measurements.In the second clinic, 1287 insemination cycles were performedusing intra-cervical insemination, timed only on basal bodytemperature. In the first clinic, a total of 53 pregnancieswere obtained, of which seven were in 55 unstimulated cycles(12.5%), 21 in 159 cycles with clomiphene citrate stimulation(13.1%, P> 0.1), and 25 in 107 cycles stimulated with clomipheneplus human menopausal gonadotrophin (HMG) (23.9%, P< 0.03).No multiple pregnancies were observed in the latter group. Inthe second clinic, 159 pregnancies occurred during 1287 inseminationcycles (12.4%). It is concluded that neither intra-uterine insemination,nor hormonal and echographic cycle monitoring, nor clomiphenecitrate enhances the success rate of artificial inseminationwith donor semen, but HMG treatment probably exerts a favourableeffect     

Andrology: Relationship between stimulated hyperactivated motility of human spermatozoa and pregnancy rate in donor insemination: a preliminary report

The proportion of spermatozoa exhibiting the vigorous motilitybehaviour termed ’hyperactivation‘ (HA) has beenshown to be increased following removal of seminal plasma andstimulation with chemical agents such as pentoxifylline. Theaim of this study was to examine the relationship between theproportion of HA in cryopreserved semen samples from sperm donorsand the corresponding pregnancy rates achieved by donor insemination.Cryopreserved samples from 20 men were incubated in the presenceor absence of 3 mM pentoxifylline for 1 h and the %HA determinedin each sample. The relationship between pregnancy rate, theproportion of HA spermatozoa in control and pentoxifyllinetreatedgroups and the change in %HA following pentoxifylline treatment(HA) as well as the mean semen characteristics for each donor[sperm count, motility (%), motility index, normal morphology(%), post-thaw motility (%) and post-thaw motility index] wereexamined by logistic regression of the occurrence of clinicalpregnancy with each insemination. Both HA and mean post-thawmotility index were significantly related to pregnancy ratesand together accounted for 64% of the observed variation inpregnancy rates.     

Prospective randomized comparison of intrauterine and intracervical insemination with donor spermatozoa

From March 1990 to September 1993, 20 women underwent a totalof 89 cycles of intracervical inseminations with donor semen(ICI) and 23 women underwent 67 cycles of intrauterine inseminationswith donor semen (IUI). The women were assigned to the two groupsrandomly, but ensuring that the ages of the women and pathologiesof the male partner (azoospermia or severe oligozoospermia)were similar in the two groups. There was no significant differencebetween the characteristics of the two groups and the methodused to induce ovulation (HMG/HCG) was identical. Two semenstraws were used for each insemination cycle. Semen was preparedfor IUI on a Percoll gradient. Thirteen clinical pregnancieswere obtained in the IUI group (19.4% of the attempts) and sixin the ICI group (6.75%). After six cycles of insemination,75.4% of the women of the IUI group obtained a pregnancy, ascompared to 35% in the ICI group. These good results may bedue to the method of induction of ovulation, but also to thetechnique itself, increasing the number of motile spermatozoaat the site of fertilization. The time taken to obtain a pregnancyis thus shorter with IUI than with ICI, and the number of semenstraws required is smaller. In-vitro fertilization (IVF) shouldbe proposed after six failures by IUI.     

Andrology: Action of pentoxifylline directly on semen

In the presence of pentoxifylline, spermatozoa can be inducedto increase certain motion characteristics. This drug capabilityhas been used to study the effect when applied directly on semen.An equal volume of pentoxifylline was added to semen, whichwas then incubated for 1 h before processing. Sperm motion wasassessed employing computer-assisted semen analysis. The resultsshowed that pentoxifylline increased curvilinear velocity, straightline velocity and lateral head displacement, the latter effectbeing concentration-dependent over the entire range of concentrationstested (r = 0.93, P < 0.0001). With a high concentrationof pentoxifylline, spermatozoa exhibited characteristics consistentwith hyperactive-like motion. Semen characteristics showed markedinter-individual variation, ranging from 0 to >40% responseto 6 mM pentoxifylline challenge. Some 10% of patients showedlittle or no response to pentoxifylline. The sum of the percentagechanges in curvilinear and straight line velocity, lateral headdisplacement and manual sperm count for each dose group wasused to produce the stimulation index, measuring the overallresponse of spermatozoa to the drug. This stimulation indexshowed that the most effective concentration was 6 mM pentoxifylline,considerably higher than the 3.6 mM pentoxifylline used commonlyfor separated spermatozoa.     

The use of urine LH detection kits to time intrauterine insemination with donor sperm

BACKGROUND: The study was carried out to determine the most likely time of day for the onset of the LH surge as detected using urine LH dipsticks, and to calculate the optimum time interval from the onset of the LH surge to intrauterine insemination (IUI). METHODS: A prospective study of 1540 cycles of IUI with donor sperm at Cleveland Fertility Centre, Middlesbrough, between June 1990 and February 2004. Only 951 cycles (where a positive urine LH dipstick result was immediately preceded by a negative result) were included in our study. To determine the best time interval between the onset of the LH surge and IUI, women were divided into five subgroups according to the positive urine test-IUI time interval and the pregnancy rate and live birth rate per cycle were calculated for each group. RESULTS: The first positive test was most frequently (44.5%) found at lunch-time (11:00-15:00). The live birth per cycle achieved was 5.6% when the insemination was performed 18-23 h from the first detection of the LH surge, and 11.7% when it was performed between 24 and 42 h. The live birth rate declined to 6.5% when IUI was performed later than that. Overall, no significant differences were discovered in live birth or pregnancy rate when insemination was performed at any of the time points between 18 and 53 h. CONCLUSION: Our study suggested that lunch-time is the best time to check for the LH surge using urine dipsticks and insemination at any time between 18 and 53 h after the onset of the surge will produce optimal results.     

A controlled study of the psycho-social development of children conceived following insemination with donor semen

Although donor insemination has been used to produce pregnanciesfor many years, there has been little information on how childrenconceived in this unusual manner develop psycho-socially. Wehave therefore carried out a controlled quantitative assessmentcomparing children who were conceived by donor inseminationto adoptees and naturally conceived children who were matchedfor age and sex. We conclude that the psycho-social developmentof donor insemination children was no different from the twocontrol groups.