A randomized prospective study to assess the effect of the use of home urinary luteinizing hormone detection on the efficiency of donor insemination.

A study was carried out to establish whether the use of home urinary luteinizing hormone (LH) detection to predict ovulation could decrease the number of clinic visits required for the management of a donor insemination (DI) cycle, and thus optimize use of clinic resources without adversely affecting pregnancy rates. This was a randomized prospective study carried out at a donor insemination clinic in Oxford, England. Fifty-six patients participated in the trial; 27 used home urinary ovulation detection for a total of 111 cycles and 29 had a total of 123 DI cycles managed by routine clinical methods. There was a significant reduction in the number of visits per cycle (P less than 0.001) if home kits for detection of ovulation were used. There was no significant difference in the monthly fecundity or cumulative conception rates. We conclude that the use of home urinary LH detection in donor insemination can reduce patient attendance at the clinic and optimize the use of medical resources without adversely affecting pregnancy rates.     

A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur.     

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.     

Intrauterine insemination: critical analysis of a therapeutic procedure.

Donor intrauterine insemination with washed spermatozoa (fresh semen) was performed in 36 women (63 cycles) whose husbands had azoospermia due to primary or secondary testicular failure. Simultaneously a control group of 76 couples (156 cycles) with proven fertility, who had recently discontinued mechanical non-hormonal contraception, were encouraged to have sexual intercourse during the fertile period. The age of the women was similar in both groups and the timing criteria were also similar. The pregnancy rate per woman was 50% in the donor insemination group and 47.4% in the control group (difference not significant). The pregnancy rate per cycle was 28.6% in the artificial insemination group and 23.1% in the control, natural insemination group (difference not significant). The number of artificial or natural insemination cycles required to achieve pregnancy was similar in the study and control groups. This study suggests that when the inseminating spermatozoa and female partner are normal, as occurs in the donor insemination group, intrauterine insemination is as efficient as natural insemination in achieving pregnancy but is not more successful.     

Infertility: Evaluation of transvaginal sonography combined with a urinary luteinizing hormone monitor in timing donor insemination

There remains controversy as to the most accurate method ofpredicting ovulation for the timing of donor insemination. Ina prospective study based at a tertiary referral donor inseminationclinic we have assessed the ability of a urinary luteinizinghormone (LH) kit combined with vaginal ultrasonography to predictovulation for donor insemination. A total of 25 natural cycleswere monitored from the first day of the LH surge (detectedby the urinary kit). Daily transvaginal sonographic measurementof follicular size and endometrial thickness were used to predictovulation; monitoring continued until post-ovulatory changeswere seen. Transvaginal sonography combined with a urinary LHkit successfully predicted all those women who ovulated (20/25)and detected unfavourable conditions for insemination in theremaining 20% (5/25). In conclusion, where available transvaginalsonography combined with a urinary LH kit should be the methodof choice for timing donor insemination.     

Lesbian mothers who conceived after donor insemination: a follow-up study

This study investigated the development of family relationshipsin lesbian families who conceived after donor insemination (DI).The main characteristics of this unknown family structure wereanalysed. An anonymous donor was used to conceive, the familyunit consisted of two mothers and a father was non-existent,and both women had a homosexual orientation. A total of 50 lesbiancouples who conceived after DI with children aged between 1and 2 years participated in this study, using a standardizedinterview created for this study. After the birth of their child,56% of the lesbian mothers (n = 100) would have wanted the identityof the donor to be registered, while 10% would have done soat the time of the insemination. Opinions differed in 12 ofthe 50 couples: the biological mother was in favour of identityregistration while the social mother was not. Both women consideredthemselves a parent of the child with equally shared responsibilities.Mothers were open about the special features of their familystructure with children and within their immediate social network.Only 30% disclosed their lesbian identity in a broader socialenvironment. The features of these newly created families mayinfluence the psychological development of the children andtherefore make long-term follow-up studies indispensable.     

Karyotype screening of potential sperm donors for artificial insemination

Cytogenetic studies were carried out in 100 potential semendonors for artificial insemination (AI) before they underwentthe routine procedures for acceptance or rejection into theprogramme, namely medical history, physical examination andblood and semen analyses. Results were only compared at theend of the study. In 80 cases, the karyotype was normal; 12males showed polymorphic chromosome variants; seven had pericentricinversions of heterochromatic regions; one had a short inversionof chromosome 2; and in one case centromere fragility was observed.Six of the 12 males with normal variants were accepted intothe programme and four of them had fathered from one to 13 normalchildren at the end of the study; the other six had been rejected,four of them because of abnormal seminograms, and another twobecause the motility control of the frozen semen was negative.Of the seven males with pericentric inversions, one droppedout of the programme; four were accepted and three of them hadproduced from two to five normal children at the end of thestudy; two had been rejected due to abnormal seminograms. Theindividual with centromere fragility was accepted and had producedfour normal children at the end of the series. Our conclusionis that although cytogenetic studies of potential donors forAI would be desirable, routine screening for chromosome anomaliesis not justified at present.     

Analysis of the attitudes and emotional processes in couples undergoing artificial insemination by donor

Osgood‘s Semantic Differential Questionnaire was usedto study 40 couples undergoing an artificial insemination bydonor (AID) programme. The following reference concepts wereused: Father, Mother, Work, Marriage, Myself, Children, Pregnancy,Guilt, Sex and Family. The results show that women consider’being a Mother‘ as something emotionally ’warm‘,take a positive position, feel ’nervous‘ and wishthe event happened quickly; this is significantly differentto men, who give less importance to this fact. Men are moreconcerned about the pregnancy and consider it a ’hard‘,’strong‘ and ’heavy‘ experience. Thescore in the concept Guilt significantly stands out from therest of the concepts in both men and women; it is also strikinghow AID women relate the concept Mother with the concept Father,whereas men establish the association between Mother and Work.     

School-aged children of donor insemination: a study of parents' disclosure patterns

BACKGROUND: A major concern in relation to donor insemination (DI) is whether children should be told about their genetic origins. This study compared the thoughts, feelings and experiences of DI parents who were inclined towards openness with those who were inclined towards non-disclosure. METHODS: Forty-six families with a 4- to 8-year-old DI-conceived child were interviewed about their decision, their reasons and subsequent concerns regarding disclosure. RESULTS: Thirty-nine percent of parents were inclined towards disclosure whilst the remaining 61% were not. The two main reasons for favouring disclosure were to avoid accidental discovery and a desire for openness. Non-disclosing parents felt that there was no reason to tell and wished to protect family members. The children who had been told reacted with either curiosity or disinterest. CONCLUSIONS: In spite of donor anonymity, parents who were intending to tell their child in the future had optimistic expectations of their child's reaction. Parents who had already told their child generally described the telling experience as a positive one.     

Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa

A randomized trial was carried out comparing recombinant FSH (rFSH) and highly purified urinary FSH (uFSH) in intrauterine insemination (IUI) with husbands' spermatozoa. A total of 45 women received rFSH (139 cycles), while 46 women received uFSH (155 cycles). The starting dose was 150 IU/day s.c., beginning on the second day, and on days 6-7 the dose was adjusted according to ovarian response, assessed by vaginal ultrasound and plasma oestradiol concentration. The pregnancy rate according to the intention to treat was 57.8% in rFSH versus 52.2% in uFSH, the corrected pregnancy rates 56.8% and 52.2%, and the cumulative pregnancy rates 69.6% and 61.0%, but the differences were not statistically significant. The per cycle pregnancy rate was 18.12% in rFSH and 15.48% in u-FSH, also not statistically significant. In the rFSH group, the consumption of FSH ampoules per cycle was significantly lower (19.20 +/- 7.02 versus 23. 80 +/- 10.78; P < 0.0001). The ratio of oestradiol/FSH ampoules was significantly higher in rFSH (56.45 +/- 31.26 versus 46.41 +/- 29. 25; P < 0.001). These data indicate that, in IUI cycles, rFSH has a higher potency than uFSH.     

The treatment of infertility by the high intrauterine insemination of husband's washed spermatozoa

A total of 345 couples with non-tubal infertility on an IVFwaiting list underwent 702 treatment cydes involving daily intrauterineinseminatlons of husband's washed spermatozoa (AIH) over 3 daysof the periovulatory period, following ovarian stimulation.Pregnancy rates achieved were depen dent upon the underlyingInfertility disorder, with similar rates noted in those witha negative post-coltal test (15.8%) or where antispermatozoalantibodies were present in either the male (18.5%) or female(17.1%) partner. These rates were significantly higher thanfor couples with poor cervical mucus (4.7%), asthenozoospermia(0%), endonietriosis (mild, 7.7%; severe, 4.1%) or unexplainedinfertility (8.5%), while discrete oligozoospermia showed mid-rangeresults (10.3%). Preg nancy outcome revealed a high level ofearly wastage (33.3%), mainly in the blighted ovum category,however congenital abnormalities (5.6%) were not significantlyincreased. It is concluded that the procedure of Affi shouldbe considered for infertility due to poor sperm-mucus interaction,antispermatozoal antibodies and simple oligozoospermia, priorto IVF-related treatments.     

Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study

BACKGROUND: Sperm DNA integrity has been used as a new marker of sperm quality in the prediction of pregnancy. Nevertheless, no previous study has been performed by analysing the same samples that were employed in assisted reproduction. The main objective of this work was to correlate sperm chromatin dispersion (SCD), measured by the SCD test, with semen parameters and pregnancy outcome in intrauterine insemination (IUI). METHODS: A total of 100 semen samples obtained from males of couples undergoing IUI were analysed by the SCD test before and after swim-up, and the results were correlated with semen parameters and pregnancy outcome. RESULTS: SCD was negatively correlated with sperm motility in both ejaculated and processed semen. Sperm recovered by swim-up did not show a significant improvement in DNA integrity. No correlation was found between SCD and pregnancy outcome in IUI. CONCLUSIONS: DNA dispersion, as measured by the SCD test, is not correlated with pregnancy outcome in IUI.     

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.     

Prediction of over-response to ovarian stimulation in an intrauterine insemination programme.

Prediction of poor-response is of equal importance to prediction of over-response in intrauterine insemination programmes. The gonadotrophin-releasing hormone agonist (GnRHa) stimulation test (GAST) was assessed as a predictor of over-response to ovarian stimulation in 81 patients. Blood samples were taken on cycle day 2 (before and 24 h after starting the GnRHa). Day 2 and 3 samples were assayed for oestradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Linear and logistic regression analyses were used to assess age, day 2 FSH, day 2 FSH/LH, oestradiol ratio (oestradiol on day 3/oestradiol on day 2) and FSH ratio (FSH on day 3/FSH on day 2) as predictors of the number of follicles (total and > or = 14 mm), oestradiol on HCG day, and clinical pregnancy rate as appropriate. Several parameters were also compared between the patients who produced < or = 3 (> or = 14 mm) follicles (group A) and those who produced >3 (> or = 14 mm) follicles (group B). The mean +/- SEM age of the patients in the study was 32 +/- 0.4 years. The mean total dose of recombinant FSH was 800 +/- 20 IU and the mean duration of stimulation was 7.6 +/- 0.2 days. Nine (11%) and 12 (15%) patients were cancelled for poor and over-response respectively. The oestradiol ratio was significantly positively correlated with oestradiol on HCG day (P < 0.001), and with the number of mature follicles (> or = 14 mm) (P = 0.01). Age, day 2 FSH and FSH ratio were not significantly correlated with oestradiol on HCG day, total follicles and follicles > or = 14 mm. None of the above-mentioned variables was correlated with clinical pregnancy rate. Group A had significantly lower oestradiol ratio (P = 0.007), longer duration of stimulation (P = 0.002), higher total FSH dose (P = 0.001), and lower oestradiol on HCG day (P = 0.001). GAST is therefore useful in predicting the high responders to gonadotrophin stimulation.     

Intrauterine donor insemination in single women and lesbian couples: a comparative study of pregnancy rates

The outcome of intrauterine donor insemination (IUI-DI) with frozen spermatozoa was analysed retrospectively in 675 cycles in single women (n = 122; 536 cycles) and lesbian (n = 35; 139 cycles) couples. The lesbian patients were younger at the initiation of treatment (mean 34.5 years; range 26-44) than the single women (mean 38.5; range 29-47) (P = 0.005). Clinical pregnancy rate was 36% in single women and 57% in lesbians (P < 0.05), the cumulative pregnancy rate after six cycles being 47% and 70% respectively, although the outcome was similar when related to age. The miscarriage rate was higher (35%) in single women than in lesbians (15%; P < 0.05), the rate being independent of maternal age. There were no apparent differences seen between the two groups with respect to the possible effect of parity, duration of infertility, causes of infertility and type of treatment at initiation of treatment; the sole exception was that the age of lesbian women was statistically significantly younger than that of single women (P < 0.005). When corrected for age, the pregnancy rates and complications were lower and higher respectively in single women but these differences did not reach statistical significance. However, the disparity between the treatment outcomes of single women and lesbian patients of similar ages may also reflect the fact that single women are likely to have failed to conceive for a period of time prior to referral to a specialist centre for treatment.     

The role of laparoscopy in intrauterine insemination: a prospective randomized reallocation study

BACKGROUND: We questioned whether a laparoscopy should be performed after a normal hysterosalpingography before starting intrauterine inseminations (IUI) in order to detect further pelvic pathology and whether a postponed procedure after six unsuccessful cycles of IUI yields a higher number of abnormal findings. METHODS: In a randomized controlled trial, the accuracy of a standard laparoscopy prior to IUI was compared with a laparoscopy performed after six unsuccessful cycles of IUI. The major end-point was the number of diagnostic laparoscopies revealing pelvic pathology with consequence for further treatment such as laparoscopic surgical intervention, IVF or secondary surgery. Patients were couples with medical grounds for IUI such as idiopathic subfertility, mild male infertility and cervical hostility. RESULTS: Seventy-seven patients were randomized into the diagnostic laparoscopy first (DLSF) group and the same number was randomized into the IUI first (IUIF) group. The laparoscopy was performed on 64 patients in the DLSF group, 10 patients withdrew their consent from participation and three patients (3%) became pregnant prior to laparoscopy. In the IUIF group, 23 patients remained for laparoscopy because pregnancy did not occur after six cycles of IUI. From the original 77 randomized patients, 38 patients became pregnant and 16 patients dropped out. Abnormal findings during laparoscopy with therapeutic consequences were the same in both groups: in the DLSF group, 31 cases (48%) versus 13 cases (56%) in the IUIF group, P = 0.63; odds ratio (OR) = 1.4; 95% confidence interval (CI): 0.5-3.6. The ongoing pregnancy rate in the DLSF group was 34 out of 77 patients (44%) versus 38 out of 77 patients (49%) in the IUIF group (P = 0.63; OR = 1.2; 95% CI: 0.7-2.3). CONCLUSIONS:Laparoscopy performed after six cycles of unsuccessful IUI did not detect more abnormalities with clinical consequences compared with those performed prior to IUI treatment. Our data suggest that the impact of the detection and the laparoscopic treatment of observed pelvic pathology prior to IUI seems negligible in terms of IUI outcome. Therefore, we seriously question the value of routinely performing a diagnostic and/or therapeutic laparoscopy prior to IUI treatment. Further prospective studies could be performed to determine the effect of laparoscopic interventions on the success rate of IUI treatment in order to rule out completely the laparoscopy from the diagnostic route prior to IUI.     

Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study

BACKGROUND: We aimed to investigate whether sperm DNA quality may predict intrauterine insemination (IUI) outcome. METHODS: The study was designed in a prospective cohort fashion, at a tertiary centre for reproductive medicine. A total of 119 patients underwent 154 cycles of IUI. Parameters related to demography, cycle management and semen sample used for IUI were evaluated. Conventional semen parameters, morphology (strict criteria), sperm DNA fragmentation and stability [evaluated by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and acridine orange staining under both acid and acid + heat denaturing conditions respectively] were measured. The main outcome measure was clinical pregnancy, defined as ultrasonographic visualization of intrauterine gestational sac(s). RESULTS: Logistic regression analyses were done on six sets of data, including all cycles combined, cycles with washed samples, first cycle of each couple, first cycle of each couple with washed samples, cycles stimulated with gonadotrophins and finally gonadotrophin-stimulated cycles with washed samples. The number of pre-ovulatory follicles on day of hCG, the age of the woman and the percentage of sperm with acid- + heat-resistant DNA were the parameters that predicted IUI outcome in most of these data subsets. For the gonadotrophin-stimulated cycles, age of the man appeared as a predictor as opposed to that of the woman; and for the cycles within this subgroup, where the semen sample was washed, sperm DNA fragmentation and age of the man were the only two parameters to predict IUI outcome. No samples with >12% of sperm having DNA fragmentation resulted in pregnancy. CONCLUSIONS: The number of follicles, age of the woman/man and sperm DNA quality may predict IUI outcome.     

Dose-finding study of triptorelin acetate for prevention of a premature LH surge in IVF: a prospective, randomized, double-blind, placebo-controlled study

Gonadotrophin-releasing hormone agonists (GnRHa) are routinely used in IVF programmes to prevent an unwanted LH surge and consequent ovulation. Despite its widespread use in IVF, a convincing dose recommendation for GnRHa in IVF does not exist. In our opinion, the lowest possible dose of GnRHa should be used. Thus, we performed a prospective, randomized, double-blind, placebo-controlled study to determine the minimal daily dose of triptorelin acetate needed to suppress a premature LH surge during IVF treatment in a long protocol. A total of 240 women (60 in each group) was randomized to either placebo or to one of three doses of triptorelin, i.e. 15, 50 or 100 microg daily. Ovarian stimulation was performed with two or three ampoules of FSH daily. A premature LH surge occurred in 23% of placebo-treated patients, but in none of the triptorelin acetate-treated patients. There were significantly more oocytes and embryos in the 50 and 100 microg triptorelin groups. There was no dose relationship in rates of either implantation, pregnancy, ongoing pregnancy, live birth or baby take-home. In this study we showed that daily administration of 15 microg triptorelin is sufficient to prevent a premature LH surge, and that 50 microg is equivalent to 100 microg in terms of IVF results.     

A randomized trial between GIFT and ovarian stimulation for the treatment of unexplained infertility and failed artificial insemination by donor.

This study was designed to investigate the surplus effect of gamete intra-Fallopian transfer (GIFT) over ovarian stimulation alone, in patients with unexplained infertility. A total of 50 patients with unexplained infertility of at least 3 years duration, or unexplained failure of artificial insemination by donor (AID) for at least 12 cycles, meeting strict inclusion criteria, were randomly selected for either two GIFT cycles or two ovarian stimulation cycles. Ovarian stimulation was combined with timed intercourse, or timed cervical donor insemination. In 38 completed GIFT cycles, five clinical pregnancies (13.2% per cycle) occurred and in 44 ovarian stimulation cycles four clinical pregnancies occurred (9.1% per cycle). Five remaining GIFT cycles were converted into in-vitro fertilization leading to two pregnancies. Of the 50 patients suffering from unexplained infertility, the 23 who did not have AID gave rise to four pregnancies out of 39 cycles (10.3%); from the remaining 27 patients who underwent AID, seven pregnancies were achieved out of 48 cycles (14.6%). No statistical differences between GIFT and ovarian stimulation treatment were found. Therefore, the GIFT success rates can be explained at least in part, if not fully, by the effect of ovarian stimulation alone. Consequently, ovarian stimulation should be considered in unexplained infertility before more elaborate forms of assisted reproduction are used.