Donor Insemination Program Research Articles

P-059 Sperm DNA fragmentation (SDF) after cryopreservation and sperm selection: implications for clinical pregnancies and live births after intrauterine insemination with donor sperm

Abstract Study question Can SDF assessment pre-cryopreservation, post-thaw and after post-thaw sperm selection predict clinical outcome in a heterologous intra-uterine donor insemination program (IUI)? Summary answer SDF increased post-cryopreservation in donor sperm and after post-thaw density gradient without affecting clinical pregnancy, live birth and miscarriage rates. What is known already Sperm cryopreservation is effective for preservation of male fertility and facilitates the storage of donor semen, while infectious disease screening can be completed and confirmed negative. Sperm viability and motility are the most vulnerable parameters during the freeze-thaw process. Inherent reactive oxygen species may induce SDF via oxidative stress. Controversial results are reported regarding induction of SDF after cryopreservation due to differences in cryo tolerance, methods of cryopreservation and methods used to evaluate SDF. Sperm selection post-thaw is indispensable to select a normal motile fraction for insemination. Again, results are controversial regarding influence on SDF levels after sperm selection post-thaw. Study design, size, duration This was a prospective, observational study. Between March 2015 and March 2019, eighteen potential sperm donors were screened via a three step plan – semen assessment, medical assessment and serological blood tests. In accordance with the Belgian legislation (2007), a sperm donor was matched to obtain a maximum of 6 pregnancies in acceptor women/couples, allowing for more than one offspring/woman or couple. A total of 106 acceptors were matched for heterologous intra-uterine insemination. Participants/materials, setting, methods Semen samples were collected after 2-7 days abstinence and standard semen parameters analyzed within 60 mins after ejaculation. Within the same time frame SDF test was performed using TUNEL assay both before and after cryopreservation and after a two-step discontinuous density gradient centrifugation post-thaw. Samples were cryopreserved by the conventional slow freezing method using sperm freeze solution. A yield of ≥ 2 M progressive spermatozoa post-thaw after selection was sufficient to contemplate IUI. Main results and the role of chance Mean female age at first cycle was 33.9 ± 4.1 years and donor age 28.5 ± 5.6 years. Out of 429 cycles, 100 (23.3%) resulted in clinical pregnancy. Excluding three ongoing pregnancies, we counted 75 live births (17.6% of cycles or 77.3% of pregnancies), while 21 pregnancies ended in miscarriage (4.9% of cycles or 21.6% of pregnancies) and 1 resulted in stillbirth. Progressive motility (59.3 ± 12.5%) decreased significantly after cryopreservation (30.0 ± 13.2%; p < 0.001), but increased post-thaw after density gradient centrifugation (61.6 ± 16.0%; p < 0.001). On the contrary, SDF (12.0 ± 5.9%) increased post-cryopreservation (26.3 ± 14.5%; p < 0.001) and further increased after sperm selection (34.9 ± 22.1%; p = 0.04). Using multilevel mixed-effects logistic regression (Odds ratio [95%CI]), we found that female age significantly influenced clinical pregnancy (0.911 [0.847-0.981]; p = 0.01), live birth (0.894 [0.834-0.959]; p = 0.002) and miscarriage rates (1.180 [1.033-1.347]; p = 0.015). There was no significant age-adjusted effect of SDF post-thaw after density gradient selection on clinical pregnancy (1.007 [0.994-1.021]; p = 0.30), live birth (1.001 [0.988-1.014]; p = 0.84) or miscarriage (1.021 [0.997-1.046]; p = 0.08). Median time-to-live birth was 4 cycles. Analyses of time-to-live birth with mixed-effects Cox models revealed no significant association with progressive motility; SDF before or after cryopreservation and after sperm selection post-thaw. Limitations, reasons for caution Results concern a small donor population, with high normal semen parameters and should therefore be extrapolated cautiously to subfertile men with normal and subnormal semen parameters. Wider implications of the findings In a donor IUI program with strict selection on conventional sperm parameters, differences in SDF before and after cryopreservation and gradient centrifugation do not change IUI outcomes, although cryopreservation and centrifugation increase SDF. Findings could be useful for the optimization of sperm freezing and selection in different assisted reproductive procedures. Trial registration number not applicable

Factors influencing pregnancy outcome with special attention to modified slow-release insemination and a patient-centred approach in a donor insemination programme: a prospective cohort study.

A higher pregnancy rate after slow-release insemination instead of bolus injection was described in previous studies. Besides an effective medical treatment most patients wish to receive a patient-centred approach with sufficient emotional support. Does a patient-friendly approach with slow-release insemination (SRI) increase the clinical pregnancy rate (CPR) after intrauterine insemination (IUI) with donor semen? The data of an ongoing prospective cohort study were analysed investigating the results of 1995 donor inseminations in 606 women from July 2011 until December 2018. As from January 2016 the insemination procedure was performed by midwives instead of medical doctors. Instead of bolus injection of sperm a slow-release IUI was done together with a more patient-centred approach. The data of 1995 donor inseminations were analysed to study the importance of different covariates influencing IUI success. Generalized estimating equations (GEEs) were used for statistical analysis. Results of two periods (2011-2015 and 2016-2018) were examined and compared. Clinical pregnancy rates (with foetal heartbeat) following donor inseminations increased from 16.6 % to 20.8 % per cycle, a non-significant increase (p=0.061). A more patient-friendly approach with slow-release of processed semen resulted in a non-significant higher clinical pregnancy rate of 4.2 % per cycle after donor insemination.

Increasing efficiency of sperm cryobanking

Introduction: Choosing the optimal methods for sperm cryopreservation is important to increase the overall efficiency in sperm cryobanking. As the efficiency of the laboratory methodology not only entails improving sperm survival and sperm yield after cryopreservation and thawing but also maximizing the utilization of available donated sperm, it is important to control the process to maximize utility. The aim of the study was to compare two methods of sperm cryopreservation to evaluate efficiency in a donor insemination program.

Female-partnered and single women's contact motivations and experiences with donor-linked families.

What are female-partnered and single mothers' motivations and experiences at one donor insemination (DI) program with regard to contacting other families who share the same sperm donor? By and large, women reported seeking contact to obtain (i) support for their children and/or themselves, and (ii) information about shared traits and medical problems, ultimately describing a range of contact experiences, both positive (e.g. special bond created) and negative (e.g. uncomfortable encounters). There is a growing phenomenon of donor insemination families-parents and/or offspring-seeking others who share their donor (i.e. are 'donor-linked'). There is limited understanding about parental motivations and experiences-especially in the presence of a second parent-due to the methodological constraints of previous quantitative studies. Semi-structured telephone interviews were conducted with 50 donor insemination mothers (14 single, 36 female-partnered). Participants were recruited by email invitation to parent members of a family-matching service at one donor insemination program in the USA. The criterion for inclusion was having matched to at least one donor-linked family. Among the 50 mothers interviewed, all had at least one child conceived via donor insemination, who was between ages 0 and 15 years at first contact. Families matched with a median of three donor-linked families (range 1-10). Interview data were analyzed through qualitative (i.e. thematic) analysis. Overarching themes emerged of seeking contact to obtain (i) support and (ii) information about children's shared physical and psychological traits. Some wanted to increase their child's family network, through adding a sibling, but more often as extended family. Data, from partnered parents especially, revealed the challenges of balancing the boundaries of family formed without the genetic link with the perceived benefits of exploring the child's donor origins. Interviews focused on openness and information-sharing were conducted with parents from one American donor insemination program. Findings are limited to individuals who were open enough to share their experiences and able to take the time to do so. As donor-linking services become established independently (e.g. donor insemination program registries) or by the government (e.g. Victoria, Australia's Voluntary Register), these findings provide evidence that linking services are valued by individuals affected by donor conception. Caution is warranted, however, in that some participants reported mismatched expectations, both across donor-linked families and within families (e.g. between partners), suggesting the need for information and guidance both during and after matching. Overall, the range and balance of reported positives and negatives indicate that donor-linking can provide individuals with support and donor origins information-which are particularly important when these are not available elsewhere. Clark University provided support. No competing interests.

Fertility in women with minimal endometriosis compared with normal women was assessed by means of a donor insemination program in unstimulated cycles

The purpose of this study was to compare the pregnancy rate in an artificial insemination donor program in women with minimal endometriosis and in women without endometriosis. A prospective double-blinded study was conducted in women with azoospermic partners. The per-cycle pregnancy rate was 8.6% (9/104 women) in the minimal endometriosis group vs 13.3% (26/196 women) in the control group. The per-woman pregnancy rate was 37.5% (9/24 women) in the minimal endometriosis group and 51.0% (26/51 women) in the control group. Pregnancy rates were statistically similar in normal women and in women with minimal endometriosis.

The making and breaking of paternity secrets in donor insemination

This paper analyses the complex issues faced by regulators of the infertility treatment industry in response to the social and technological changes that heralded a new openness in knowledge about...

Long-term cryostorage of sperm in a human sperm bank does not damage progressive motility concentration

The use of quarantined cryopreserved semen is mandatory in donor insemination programs. Whether sperm cells can survive and retain their ability to fertilize after long-term storage remains a controversial issue. The objective of this study was to determine the effect of the duration of cryostorage in liquid nitrogen on the sperm cells' progressive motility concentration (PMC) in a large study group. A total of 2525 thawed sperm specimens, packed in straws and donated by 72 sperm bank donors for intrauterine insemination (IUI), were evaluated in an assisted reproduction institute. PMC was recorded after 0.5-14.4 years of cryostorage. The mean (+/-SD) value of PMC of all study samples was 10.8 +/- 3.3 x 10(6)/ml after freezing/thawing and before cryostorage (T0), and 12.3 +/- 2.9 x 10(6)/ml after storage and before using the specimen for IUI (T1, P < 0.0001). Specimen storage for different lengths of time revealed that storage duration had no significant influence on the PMC of the specimens (r = -0.03, P = 0.08). The PMC of partially filled straws was lower than in full straws. Cryostorage duration made no difference in the PMC of raw and washed sperm specimens. Prolonged storage of donated sperm in liquid nitrogen had no influence on the PMC of the specimens and therefore should not alter the fertilization potency of donated sperm. The high post-storage values of the PMC compared with the pre-storage PMC values was probably an artifact of the small volume of the pre-storage sample.

Contact among families who share the same sperm donor

To examine the experience of contact among families who share the same sperm donor and the purpose served by contact. Study 1: retrospective survey; study 2: archival data analysis. Donor insemination (DI) program. Study 1: 14 parents from the first cohort of matched families; study 2: Archival data about 515 families from the DI program. Study 1: Interview of parents via anonymous mail-back survey; study 2: none. Study 1: Survey questions focused on the family, contact experience, and relationship to the matched family. Study 2: Comparison of families in the matching service to DI program families on family structure, parity, and type of donor (anonymous or open-identity). Study 1: Single women and lesbian couples headed most families. Parents reported positive experiences with contact. Reasons for contact focused on creating family for the child and addressing questions about the donor. Study 2: Families with open-identity donors and those headed by single women were overrepresented in the matching service; heterosexual couple-headed families were underrepresented. Findings indicate positive outcomes for contact among families who share the same donor. Contact appears to serve the purpose of creating extended family for the child and may also help answer questions about the donor.

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

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

Optimisation des résultats d'inséminations intra-utérines uniques avec sperme de donneur : bilan de quatre ans d'activité

Our aim was to analyse the results of a donor insemination program using ovarian stimulation, swim-up sperm preparation and intrauterine insemination proposed to women with a maximum age of 39. Incidence of several clinical and biological parameters on success rates was investigated. Retrospective analysis of the results of 249 cycles performed in 106 couples during a four-year period is reported. Overall pregnancy rate of 28.1% and delivery rate of 22% per cycle were achieved, with a multiple pregnancy rate of 11.4%. Most of the pregnancies (84%) were obtained before the fourth insemination. Among the different parameters studied the total number of motile sperm inseminated was found to be the most important factor for success rate: pregnancy rate per cycle reached 40.4% if more than 1.5 million progressive sperm were inseminated vs. 24.7% if they were less than 1.5 million (P<0.05). In precise conditions, outcome of inseminations with donor semen can reach satisfying pregnancy rates, being a valuable help for couples suffering of long-time infertility.

Optimization of the Donor Insemination Program: A Variation on the Theme

Optimization of the Donor Insemination Program: A Variation on the Theme

Adolescents with open-identity sperm donors: reports from 12–17 year olds

Donor insemination programs can include 'open-identity' sperm donors, who are willing to release their identities to adult offspring. We report findings from adolescent offspring who have open-identity donors. Using mail-back questionnaires, youths from 29 households (41.4% headed by lesbian couples, 37.9% by single women, 20.7% by heterosexual couples) reported their experience growing up knowing how they were conceived and their interest in the donor's identity. Most youths (75.9%) reported always knowing, and were somewhat to very comfortable with their conception origins. All but one felt knowing had a neutral to positive impact on their relationship with their birth mother and, separately, co-parent. The youths' top question about the donor was, 'What's he like?' and >80% felt at least moderately likely to request his identity and pursue contact. Finally, of those who might contact the donor, 82.8% would do so to learn more about him, with many believing it would help them learn more about themselves. No youth reported wanting money and few (6.9%) wanted a father/child relationship. We also discuss differences found among youths from different household types. The majority of the youths felt comfortable with their origins and planned to obtain their donor's identity, although not necessarily at age 18.

Seminal lead concentrations negatively affect outcomes of artificial insemination

Objective To determine the relationships among seminal lead levels, acrosome status, and artificial insemination cycle fecundity (AI f) in semen donors. Design Longitudinal analysis of seminal lead levels, sperm function testing, and fecundity. Setting University medical center andrology and research laboratories. Patient(s) Semen donors (n = 15) participating in a therapeutic donor insemination program. Intervention(s) None Main outcome measure(s) Seminal plasma lead levels, acrosome sensitivity to progesterone (P) and voltage-gated potassium channel inhibitors (e.g., charybdotoxin [CBTx]), and AI f. Result(s) Seminal plasma lead levels and AI f were strongly negatively correlated. Semen donors were divided into three groups by acrosome response to P: normal (CBTx sensitive [Rs] or CBTx resistant [Rr]: responders) and reduced ( nonresponders [NR]) (Rs > Rr >> NR). Seminal lead differed among the three groups (NR > Rr > Rs). Comparison of 330 artificial insemination cycles from four Rs, four Rr, and two NR demonstrated that cycle AI f also differed significantly between groups (Rs >Rr >>NR). Conclusion(s) Measurements of seminal plasma lead, P-stimulated acrosome loss, and sensitivity to CBTx may provide prognostic information on the fertility status of potential donors as well as male infertility patients. Such evaluations may assist in donor acceptance, or in the case of patients, in selection of the appropriate treatment regimen.

Oocyte donation using cryopreserved donor oocytes

Objective: The use of cryopreserved semen in donor insemination programs is now mandatory in most countries to minimize the transmission of HIV and other diseases to recipients. Previously, cryopreserved oocyte donation has not been practical due to the low efficiency of oocyte cryopreservation itself. We report here our encouraging results on oocyte donation using cryopreserved donor oocytes from our oocyte bank. The survival, fertilization, implantation, and pregnancy rates were analyzed and compared to those of sibling fresh oocytes and cryopreserved embryos obtained from the same cycles.

A comparison of intrauterine versus intracervical insemination in fertile single women

Objective: To compare the efficacy of intrauterine insemination (IUI) and intracervical insemination (ICI) when used by fertile single women in a donor insemination program. Design: Prospective randomized crossover study. Setting: Donor insemination program (not an infertility clinic). Patient(s): Single fertile women choosing to inseminate with frozen donor semen. Intervention(s): Clients received procreative counseling and screening and were then randomly assigned to begin office insemination with ICI or IUI. If additional insemination cycles were required, the clients used the method opposite their previous method of insemination until pregnancy was achieved. Main Outcome Measure(s): Monthly fecundity rate was compared between the two methods of insemination. Result(s): Sixty-two women contributed a total of 189 cycles, 94 by IUI and 95 by ICI. The monthly fecundity rate for IUI was 15%, as compared with 9% for ICI, ( P=0.14). When the analysis was confined to cycles in which only one insemination was performed (64 IUI and 65 ICI cycles), the monthly fecundity rates were 14% for IUI and 5% for ICI ( P=0.04). Conclusion(s): Intrauterine insemination with frozen donor sperm is more effective than intracervical insemination for single women without known fertility problems.

Why Leave a Donor Insemination Program Before Conceiving?

Objective: Success rates with donor insemination (DI) are high compared to other forms of assisted reproduction (e.g., IVF) and the financial costs relatively low. Nonetheless, a significant proportion of recipients leave prior to conceiving. This study identified factors related to leaving a DI program prior to conceiving.

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.

Fecundability trends among sperm donors as a measure of donor performance

Objective: To examine fecundability trends among sperm donors. Design: Retrospective analysis. Setting: University-based sperm bank and donor insemination program. Patient(s): Sperm donors and recipients. Intervention(s): A group of recipients underwent IUI with cryopreserved donor sperm. Fecundability was calculated for 20 sperm donors over 800 insemination cycles. Main Outcome Measure(s): Average fecundability per donor was compared for the first 40 cycles of a donor’s use and for those donors within a group of more fertile recipients. Sperm parameters, recipient ages, and number of unique recipients for each donor were analyzed. Result(s): Average donor fecundability is constant; however, individual donors demonstrated differences among their fecundabilities (overall mean, 0.09; range, 0.01–0.26). These differences persisted for donors among a group of more fertile recipients (overall mean, 0.12; range, 0.02–0.35). A donor’s fecundability at 15 cycles is predictive of his future performance. Conclusion(s): Differences in fecundability exist among sperm donors which cannot be discerned through routine semen parameters. Sperm donor fecundability should be analyzed periodically, and directors of sperm banks should consider discontinuing use of a donor whose outcome is substandard.

Sperm output of healthy men in Australia: magnitude of bias due to self- selected volunteers

Controversial claims, based on a meta-analysis aggregating 61 heterogeneous observational studies, have been made that human sperm output has decreased by 50% over the last six decades and that this trend may be due to global pollution. If true, such effects should be evident in all areas of the globe; however, longitudinal studies within single centres in Europe and America have produced conflicting results and there are no reports from the southern hemisphere. We therefore reviewed semen analyses obtained from 1980-1995 from 689 healthy men volunteering for screening either as potential sperm donors for a donor insemination programme (n = 509) or to participate in five male contraception research studies (studies no. 1-5, n = 180). All were recruited through the Andrology Unit of the Royal Prince Alfred Hospital, Sydney, by the same doctors using standard methods of recruiting, screening and laboratory examination throughout the period 1980-1995. Recruitment was by advertising without regard to marital or fertility status except in two contraceptive efficacy studies (no. 1 and no. 3) where participants had to be in a stable relationship requiring contraception. Analysing the first semen sample individually or when grouped by year of ejaculation, there was no significant difference in sperm concentration over time or between years or according to year of birth. During the second half of this period, 180 consecutive volunteers were recruited by the same doctors and staff for five male contraception studies. The median sperm concentration for studies no. 1 (103 x 10(6) ml) and no. 2 (142 x 10(6) ml) were significantly (P < 0.05) higher than for studies no. 3-5 (84, 67 and 63 x 10(6) ml, respectively) and for potential sperm donors (median 69 x 10(6) ml). The inconsistency of these estimates illustrates the magnitude of bias (up to 100%) in sperm output that may occur in recruiting groups of self-referred volunteers within a single centre. This highlights the invalidity of extrapolating similar findings on sperm output of self-selected volunteers to the general male community or in using such study groups to characterize sperm output in supposedly 'normal' men.

The Total Motile Sperm Count and Linear Progression of Post-Washed Samples are Independent Predictors of Pregnancy in a Frozen Donor Insemination Program

The Total Motile Sperm Count and Linear Progression of Post-Washed Samples are Independent Predictors of Pregnancy in a Frozen Donor Insemination Program