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PubMed1998

Comparison of two methods of assisted fertilization in cynomolgus monkeys (Macaca fascicularis): intracytoplasmic sperm injection and partial zona dissection followed by insemination.

Intracytoplasmic sperm injection (ICSI) and partial zona dissection followed by insemination (PZD-I) were used to establish a microinjection system in cynomolgus monkeys (Macaca fascicularis), which are potential models for human reproduction. Two experimental systems were studied, in which either hamster oocytes or cynomolgus monkey oocytes were used as the vehicle. When hamster oocytes were used, 66 out of 81 ICSI-treated oocytes (82%) showed sperm head swelling or pronucleus formation. Following PZD-I of hamster oocytes the rates of spermatozoa penetration (85/114; 75%) and fertilization (71/114; 62%) were relatively high. When cynomolgus monkey oocytes were used, 19 out of 31 (61%) were fertilized by ICSI with cynomolgus monkey spermatozoa and, subsequently, two embryos (7%) developed to the morula stage. In total, 94% (15/16) of the PZD-I treated oocytes were penetrated by spermatozoa and 63% (10/16) were fertilized. These results demonstrate that both micromanipulation techniques can be used in assisted fertilization with cynomolgus monkeys.

Animals↗
PubMed1998

Artificial insemination by husband in unexplained infertility compared with infertility associated with peritoneal endometriosis.

There have been numerous inconclusive studies examining the differences between unexplained and peritoneal endometriosis-associated infertility. Hence, the choice of artificial reproductive technique may be difficult. This prospective study compares outcome in couples with unexplained infertility and with minimal or mild endometriosis-associated infertility, undergoing treatment with ovarian stimulation combined with artificial insemination by husband. No differences were found between the unexplained infertile and the endometriosis group as to patient characteristics, response to ovarian stimulation and semen qualities. There was a significantly higher total pregnancy rate, with more multiple gestations, in the unexplained infertile compared with the endometriosis group. The difference in outcome could reflect differences in pathogenesis and aetiology for the two groups.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome.

A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.

Clomiphene↗
PubMed1999

Is waiting for an endogenous luteinizing hormone surge and/or administration of human chorionic gonadotrophin of benefit in intrauterine insemination?

This retrospective study was undertaken to investigate the observation that the probability of pregnancy was higher with intrauterine insemination (IUI) when human chorionic gonadotrophin (HCG) was administered after the onset of the luteinizing hormone (LH) surge. A total of 219 patients who had 524 IUI cycles was included in this study. IUI cycles were divided into three groups: group 1, patients who had an endogenous LH surge but no HCG; group 2, patients given HCG after an endogenous LH surge was observed; and group 3, patients given HCG before an endogenous LH surge could be demonstrated. The overall clinical pregnancy rate was 16%. Forty-two (19.2%) patients had 91 cycles with their partner's semen, while 177 (80.8%) used donor semen in 433 cycles; clinical pregnancy rates were 12.1% and 16.9% respectively. There was no significant difference in pregnancy rate per cycle between patients in group 1 (12.7%) compared with those in groups 2 (15.6%) or 3 (20.5%). We could not establish any benefit in waiting for a spontaneous LH surge before administering HCG in the presence of a mature follicle(s) in this study. This strategy avoids further monitoring to detect the LH surge, allowing treatment to be planned for a time convenient to the patient.

Adult↗
PubMed1999

Early resort to ovarian stimulation improves the cost-effectiveness of a donor insemination programme.

Women undergoing donor insemination (DI) are usually regularly ovulating, therefore the role of ovulation induction in this modality of treatment has been controversial. Some recent studies reported higher pregnancy rates in stimulated cycles in comparison with natural cycles. We employed a sequential step-up protocol in which treatment was started in a natural cycle, continued with a clomiphene citrate-stimulated cycle, and finished with an ovulation induction cycle. The patients were allowed three attempts at each step before moving to the next if conception did not occur. The aim of this protocol was to enhance the cost-effectiveness of the DI programme by increasing the cycle fecundability. A total of 101 patients underwent 216 cycles of DI, including 44 patients in 80 natural cycles, 38 patients in 89 CC-stimulated cycles, and 19 patients in 47 ovulation induction cycles. The clinical pregnancy rate per started cycle (CPR/C) and per patient during this period was 14% and 30% respectively. The pregnancy rates per started cycle and per patient in the natural, CC-stimulated and ovulation induction cycles were: 13 and 32%, 10 and 18%, and 21 and 53% respectively. There was no significant difference in the CPR/C in the three groups; however, the CPR per patient in the induced ovulation cycles was significantly higher than in the CC-stimulated cycles (P = 0.005). Only one patient during this period had a multiple pregnancy in the ovulation induction group, giving an overall multiple pregnancy of 3%. By using this treatment strategy, we achieved a high clinical pregnancy rate, a low multiple pregnancy rate and a low cost of treatment per pregnancy.

Adult↗
PubMed1999

Obstetric and perinatal outcome of pregnancies after intrauterine insemination.

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

Adult↗
PubMed2000

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.

Abortion, Spontaneous↗
PubMed2000

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.

Adolescent↗
PubMed2000

What does it mean to be a donor offspring? The identity experiences of adults conceived by donor insemination and the implications for counselling and therapy.

In the absence of research with adult donor offspring, this study begins to bridge that gap by asking individuals about their experiences as donor offspring and considering the implications for psychotherapeutic and counselling practice. Sixteen participants (13 male, three female, age range 26-55 years) recruited through donor insemination support networks in the UK, USA, Canada and Australia, were sent semi-structured questionnaires by E-mail and post. Using identity process theory as a framework for understanding participants' accounts, the data were qualitatively analysed using interpretative phenomenological analysis. Participants consistently reported mistrust within the family, negative distinctiveness, lack of genetic continuity, frustration in being thwarted in the search for their biological fathers and a need to talk to a significant other (i.e. someone who would understand). These experiences could be postulated as being indicative of a struggle to assimilate, accommodate and evaluate information about their new identities as donor offspring. Psychotherapists and counsellors need to be aware of these identity issues if they are to meet the needs of donor offspring within therapeutic practice.

Adult↗
PubMed2000

Disclosure of donor insemination to the child: the impact of Swedish legislation on couples' attitudes.

The question whether or not parents of children conceived after donor insemination (DI) tell their offspring about its biological background was addressed. Swedish legislation from 1985 gives the child born after DI the right, when grown up, to receive identifying information about the sperm donor. Until now no information about compliance with the law has been available. All parents who gave birth to a child by DI after the new legislation in two major Swedish fertility centres (Stockholm and Umeâ) received a questionnaire containing questions about the issue of informing the child. The response rate was 80%. The majority of parents (89%) had not informed their children, whereas 59% had told someone else. As a response to an open question, 105/132 parents chose to comment on their answer about not having informed their child. Of these families, 61 intended to tell their child later, 16 were not sure and 28 were not going to inform the child. Compliance with the law must be regarded as low since only 52% of the parents had told or intended to tell their child. In addition, concern is raised about the children who run the risk of being informed by someone other than their parents.

Adolescent↗
PubMed2001

Results of 6139 artificial insemination cycles with donor spermatozoa.

BACKGROUND: Artificial insemination by donor spermatozoa (AID) can prove a valuable treatment for a number of male factor disorders, although its success rate is variable. METHODS: Retrospective analysis of the results of 6139 cycles performed in 1001 women during an 18 year period is presented. Pregnancy rates per cycle are presented as a function of: female fertility history, treatment modalities, medication used for induction of ovulation, female age, year of treatment, consecutive cycle effect and the use of fresh versus frozen-thawed spermatozoa. RESULTS: Overall pregnancy rate of 12.6% and cumulative pregnancy rate after 12 months of treatment of 75% were achieved. Age was found to be the most important determinant for success rate. CONCLUSIONS: Since the establishment of AID treatments, the mean age of the population of women receiving treatment has increased each year. Consequently, success rate did not improve, even with the use of more sophisticated medical modalities.

Abortion, Spontaneous↗
PubMed2001

Perifollicular vascularity as a potential variable affecting outcome in stimulated intrauterine insemination treatment cycles: a study using transvaginal power Doppler.

BACKGROUND: The aim of the present study was to assess any potential relationship between perifollicular vascularity and outcome in an in-vivo environment following human chorionic gonadotrophin (HCG) administration. METHODS: A total of 182 unselected consecutive patients undergoing stimulated intrauterine insemination (IUI) cycles was recruited where the perifollicular vascularity of follicles > or =16 mm was studied using a subjective grading system and transvaginal power Doppler ultrasonography, 36 h after HCG administration. RESULTS: A total of 601 follicles was studied. The incidence of follicles showing high-grade perifollicular vascularity (3 and 4) was higher than those with low-grade vascularity (1 and 2) (80 versus 20%). Treatment cycles were divided according to uniformity of vascularity grades of follicles > or =16 mm on the day of IUI [55% all high (3/4) grade; 33% mixed (1/2 and 3/4) and 12% all low (1/2) grade]. The mean age and duration of subfertility were significantly higher (P < 0.05), whereas the number of follicles > or =16 mm pre/post HCG, serum oestradiol and incidence of ultrashort gonadotrophin-releasing hormone (GnRH) agonist use were all significantly lower (P < 0.05) in treatment cycles with uniformly low follicular vascularity grades compared with mixed or uniformly high-grade cycles. However, on subjecting the data to multiple logistic regression analysis, the only independent variables that affected pregnancy rates appeared to be serum oestradiol (OR 1.28, 1.01--1.62) and high-grade follicular vascularity (OR 2.41, 1.08--5.40). CONCLUSION: These data would suggest that perifollicular vascularity has an important role to play in the outcome of IUI cycles, and that power Doppler has the potential to refine the management of assisted reproduction treatment cycles.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

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.

Australia↗
PubMed2002

Reduction of steps in the preparation of motile sperm for intrauterine insemination does not reduce efficacy of the procedure: simplified one-step swim-up method versus classic swim-up.

BACKGROUND: Intrauterine insemination (IUI) is a valid treatment for infertility with a cumulative pregnancy rate of >40-90% after 3-10 treatment cycles. We studied the efficacy of a simplified method for motile sperm preparation for IUI. METHODS: A prospective clinical trial was performed with 100 couples (male age 33-48 and female 28-37 years) with a 2-8 year history of primary infertility associated with slight oligozoospermia (16/100), oligomenorrhoea (32/100) or unknown (52/100). Motile sperm for IUI were prepared by: (A) the classic World Health Organization self-migration (swim-up) method which includes centrifugation, or (B) a simplified one-step swim-up procedure without centrifugation. Recombinant FSH was used for ovarian stimulation. Depending on the cause of infertility, patients were matched one-to-one at the time of IUI, so that when a total of 100 couples had been treated, 50/100 women received sperm prepared by method A and 50/100 by method B. RESULTS: A statistically significant correlation was found between the percentage motile sperm of the original semen sample and the percentage of motile sperm recovered by method A (r = 0.333, P < 0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P < 0.001) was found between the two methods. CONCLUSIONS: The simplified one-step swim-up method was as effective as the classic swim-up method, but the former was easier and more economical.

Adult↗
PubMed2003

Investigation of the infertile couple: should diagnostic laparoscopy be performed in the infertility work up programme in patients undergoing intrauterine insemination?

Diagnostic laparoscopy is normally the standard procedure performed as the final test in the infertility work up before progressing to infertility treatment. Recently, there has been a growing tendency to bypass diagnostic laparoscopy after a normal hysterosalpingogram and instead to start direct infertility treatment [intrauterine insemination (IUI) or IVF] for indications such as unexplained infertility, male subfertility and cervical hostility. In our clinic, laparoscopy revealed abnormalities that resulted in changed treatment decisions in 25% of the patients who would normally have been scheduled for IUI if laparoscopy had not been performed. The changed treatments mainly concerned surgery for minimal/mild endometriosis and periadnexal adhesions, both performed during the diagnostic laparoscopy. Because the effect of such interventions on the success rate of IUI has never been described, it still remains unclear whether laparoscopy is usefully performed in these cases. Therefore, further prospective studies should be performed to assess whether delaying, or bypassing entirely, diagnostic laparoscopy is more cost effective and if laparoscopic interventions for intra-abdominal abnormalities are effective in terms of higher pregnancy rates after treatment with IUI.

Endometriosis↗
PubMed2003

The significance of the ionophore-challenged acrosome reaction in the prediction of successful outcome of controlled ovarian stimulation and intrauterine insemination.

BACKGROUND: This prospective study compared the acrosome reaction following ionophore challenge (ARIC) versus conventional sperm parameters and sperm velocities in predicting successful outcome following ovarian stimulation and intrauterine insemination. METHODS: All patients were offered a maximum of three treatment cycles. Conventional semen analysis was performed and sperm velocities were measured using computer-aided sperm analysis. Acrosome-reacted sperm were stained using chlortetracycline after ionophore challenge. Multiple logistic regression analysis and the receiver-operator characteristic curve analysis were applied to determine the best predictive variables and their cut-off values. RESULTS: ARIC score was the most significant variable in predicting pregnancy, followed by the percentage of induced acrosome-reacted sperm, serum estradiol levels on the day of hCG and sperm morphology by strict criteria. Higher spontaneous acrosome reaction had a negative relationship with pregnancy. ARIC score of 10% had a sensitivity of 85.3% and a specificity of 85.5%. The positive and negative predictive values were 64.2 and 96.6% respectively and the false positive and negative rates were 14.7 and 14.5% respectively. CONCLUSION: ARIC score was a better predictor of pregnancy than conventional sperm parameters and sperm velocities.

Acrosome Reaction↗