Intrauterine insemination-ready versus conventional semen cryopreservation for donor insemination: a comparison of retrospective results and a prospective, randomized trial.

OBJECTIVE: To compare fecundity rates following intrauterine insemination (IUI) with donor sperm frozen conventionally versus an IUI-ready preparation. DESIGN: Both retrospective results and a prospective, randomized study where recipients were assigned to one of two sperm cryopreservation methods in each cycle of intrauterine insemination are reported. SETTING: University-based infertility practice, affiliated private practices, and andrology laboratory. PATIENT(S): Women desiring therapeutic insemination in an effort to establish pregnancy. INTERVENTION(S): Intrauterine insemination with donor sperm frozen conventionally or by an IUI-ready protocol. MAIN OUTCOME MEASURE(S): Cycle fecundity in donor IUI recipients. RESULT(S): In a retrospective analysis involving 642 inseminations in 209 recipients, 79 pregnancies were recorded for an overall pregnancy rate of 12.3% per insemination (or cycle): 11.3% with IUI-ready sperm and 13.9% with conventionally preserved sperm. In a follow-up prospective, randomized study, the pregnancy rate for IUI-ready sperm preparations was 36% per cycle (14 of 39) whereas that for conventionally preserved sperm was 19.6% per cycle (9 of 46). Thirteen of the 23 pregnancies occurred in the first study cycle of insemination; only two pregnancies were observed in patients undergoing more than four cycles of insemination. CONCLUSION(S): Cycle fecundity for IUI-ready donor sperm is equivalent to conventional cryopreserved sperm based on both prospective and retrospective assessments.     

Predictors of success with the use of donor sperm

OBJECTIVE: This study was undertaken to assess the effect of multiple factors that influence the success rate and time to conception among couples undergoing donor sperm insemination. STUDY DESIGN: A retrospective analysis of 960 cycles of frozen donor sperm insemination was performed at the University of Florida. Cycle pregnancy rates and cumulative probability of pregnancy were compared using several variables. RESULTS: The pregnancy rate was 12.1% per treatment cycle, and the cumulative probability of pregnancy exceeded 80% for the entire cohort. Seventy percent of pregnancies resulted in a liveborn infant. Age had a profound impact on the cycle pregnancy rate. The cycle pregnancy rates for women younger than 30 years, between the ages of 30 and 35 years, between the ages of 35 and 40 years, and older than 40 years were 15.8%, 14.6%, 8.2%, and 0%, respectively. There was a trend toward higher cycle pregnancy rates in women with prior pregnancies versus women without prior pregnancies of 14.4% and 12.3%, respectively. Parity had no effect on the cycle pregnancy rate or the cumulative probability of pregnancy. There was a trend toward higher cumulative probability of pregnancy in women whose partners were azoospermic versus oligospermic. There was no difference in pregnancy rates obtained with the Percoll wash gradient versus the Isolate gradient. At >20 million total motile sperm per insemination, there was no threshold above which the pregnancy rate was improved. CONCLUSION: The most significant influence on pregnancy rates in the donor sperm insemination program at the University of Florida was maternal age. Nulligravidity and a diagnosis of mild oligospermia in the man may have a negative impact on pregnancy rates.     

Effectiveness of stimulated menstrual cycles and Percoll sperm preparation in intrauterine insemination

To examine the usefulness of intrauterine insemination in women with various fertility factors, we retrospectively analyzed data from women treated during 1986 and 1987. Ninety-three patients underwent 1-11 cycles of single or double procedures, for a total of 423 inseminations in 263 treatment cycles. Twenty-six patients (28%) conceived, for a 10% total pregnancy rate per cycle, with 58% of the pregnancies resulting from double inseminations per cycle. An average of two treatment cycles was required to achieve pregnancy. Eight pregnancies (31%) occurred in spontaneous cycles, while 18 (69%) occurred in stimulated cycles. While clomiphene citrate therapy was useful in anovulatory patients, it was of no benefit in ovulatory patients being treated with intrauterine insemination. Human menopausal gonadotropin therapy was of benefit in both ovulatory and anovulatory patients when combined with intrauterine insemination. The live birth rate was higher (75%) in spontaneous cycles than in stimulated cycles (44%). Semen preparation was accomplished by sperm washing in 61% of the pregnancies and by Percoll preparation in 39%. The effectiveness of the discontinuous Percoll gradient for semen preparation for insemination was suggested by a pregnancy rate of 9% per cycle. While the mean sperm count in the pregnant group was 44 million, successful pregnancy was accomplished with a double insemination of 880,000 and 1.16 million rapidly progressive sperm in the first and second inseminate, respectively. The data confirm the important role of intrauterine insemination for the treatment of infertility.     

Intrauterine insemination: the University of Minnesota experience

Forty-five patients initiated intrauterine insemination between October 1981 and August 1983. Indications for insemination included poor semen (count less than 20 X 10(6)/ml and/or motility less than 40%), poor cervical mucus, presence of sperm antibodies, unexplained poor postcoital tests, or various combinations of the above. During this time period, 374 inseminations were performed in 163 cycles and resulted in eight pregnancies in the 45 patients receiving artificial insemination by homologous donor, for an overall pregnancy rate of 17.4%. The fact that five of the pregnancies occurred in the first insemination cycle and two in the second cycle was felt to indicate a cause-and-effect relationship. A trial of intrauterine insemination in selected patients would appear to be warranted.     

Success of intrauterine insemination using cryopreserved donor sperm is related to the age of the woman and the number of preovulatory follicles

Objective: Our objective was to assess parameters associated with a successful outcome of intrauterine insemination (IUI) using cryopreserved donor sperm. Design: We analyzed 750 consecutive donor IUI cycles undertaken by 363 women in an assisted conception clinic. The main outcome measure was clinical pregnancy. Results: IUI was performed in 94.7% of the 750 IUI treatment cycles commenced and 180 clinical pregnancies occurred. The clinical pregnancy rate per cycle was 26.4%. The rate was significantly related to the patient's age (30.5% for age 35 years and 18.1% for age >35 years;P<0.006) and whether there was one or more than one preovulatory follicles [20.9, 34.4, and 31.5% for one, two, and three or four follicles with a mean diameter of 14 or more mm at the time of human chorionic gonadotropin (hCG) administration;P=0.006]. Two to four preovulatory follicles were present in 12.6% of the natural cycles, 43.6% of clomiphene citrate or tamoxifen, and 59.9% of gonadotropin stimulated cycles. The difference in the number of preovulatory follicles between stimulated and unstimulated cycles was highly significant (P<0.0001). Pregnancy rates were 29.9% in gonadotropin-stimulated cycles, 23.6% in clomiphene citrate- or tamoxifen-stimulated cycles, and 20.1% in unstimulated cycles. The difference in pregnancy rates between gonadotropin-stimulated and natural cycles was significant (P=0.038). Cycle fecundity rates were not significantly affected by the number of previous treatment cycles, duration of infertility, gravidity and parity of the patient, presence of a spontaneous luteinizing hormone (LH) surge before the administration of hCG, or number of motile sperm in the insemination specimen. Conclusions: Success of IUI using cryopreserved donor sperm is related to the age of the women and whether there is one or more than one preovulatory follicles.     

Comparison of fecundability with fresh and frozen semen in therapeutic donor insemination

A series of 401 therapeutic donor insemination (TDI) cycles was analyzed for determining the effect on fecundability of fresh versus cryopreserved semen, the number of inseminations per cycle, recipient age, and the reproductive health of the TDI recipient. We followed a protocol in which inseminations were performed during the periovulatory period determined by urinary luteinizing hormone surge or ultrasound-timed human chorionic gonadotropin injection. The minimum standard for insemination with fresh or cryopreserved semen was a total of 40 X 10(6) grade 3 sperm. We found no decreased fecundability when using frozen semen, rather than freshly ejaculated specimens. The number of inseminations per cycle did not affect the pregnancy outcome after TDI. The reproductive health of the recipient had a significant effect on the pregnancy rate. Fecundability was 15.6% for healthy women, as compared with 6.7% for women with a diagnosis of moderate, severe, or extensive endometriosis, pelvic adhesions, tubal disease, or ovulatory dysfunction. To avoid transmission of human T-lymphotropic virus type III from sperm donor to TDI recipient, we have recently utilized an exclusively frozen TDI program. With well-timed inseminations of 40 X 10(6) grade 3 motile sperm, we have been able to attain pregnancy rates similar to those previously obtained with fresh samples.     

Intrauterine insemination as treatment for antisperm antibodies in the female

Ninety-one women with long-standing infertility in the presence of humoral antisperm antibodies (ASA) underwent 473 cycles of intrauterine insemination of washed sperm (IUI), resulting in 26 pregnancies. Nine pregnancies were achieved in 67 women who underwent 285 IUI during unstimulated cycles (13% pregnancy rate; 3% pregnancy/cycles of treatment). Twenty women underwent 86 IUI after clomiphene citrate (CC) stimulation, resulting in 6 pregnancies (30%; 7% per cycle), while 28 underwent 102 cycles of IUI after human menopausal gonadotropins (hMG) stimulation, resulting in 11 pregnancies (39%; 11% per cycle). Twenty-one of the 26 pregnancies (81%) were achieved in the first 2 IUI cycles. During unstimulated and CC IUI cycles, all pregnancies occurred in the first two cycles of treatment, while with hMG stimulation pregnancies also occurred in the third, fourth, and fifth IUI cycles. Nine of these 91 women subsequently conceived spontaneously, and three others conceived through in vitro fertilization. Only 6 of the 38 pregnancies resulted in spontaneous abortion (16%). Thus, pregnancies achieved in women with ASA have no increased risk of abortion.     

One versus two inseminations per cycle in intrauterine insemination with sperm from patients' husbands: a systematic review of the literature

OBJECTIVE: To study the efficacy of performing two inseminations per cycle in IUI with husband's sperm compared with one insemination per cycle. DESIGN: Meta-analysis. SETTING: Randomized and prospective trials comparing two inseminations vs. one insemination per cycle in IUI with husband's sperm, retrieved by MEDLINE and Cochrane Library searches (1966-2001) and a manual search of the abstracts of the European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine annual meetings (1990-2001). PATIENT(S): A total of 865 patients underwent 1156 cycles of IUI with husband's sperm. INTERVENTION(S): After different ovarian stimulation protocols, one or two inseminations were performed. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle. Detected studies were tested for homogeneity. Because heterogeneity was observed, DerSimonian-Laird relative risk with alleatory effects was used. RESULT(S): Six randomized and prospective trials involving 865 patients and 1156 cycles were identified. There was remarkable heterogeneity among the different studies concerning methodology, especially regarding ovarian cycle management and the timing of inseminations. Although the pregnancy rate per cycle was somewhat higher in the two-inseminations-per-cycle group (14.9% vs. 11.4%), there were no statistically significant differences (relative risk = 1.34; 95% confidence interval 0.90-1.99). CONCLUSION(S): No significant differences were observed when two inseminations per cycle were performed, compared with one insemination. There was great heterogeneity concerning ovarian management and insemination timing. This heterogeneity hampered the analysis. We detected a better pregnancy rate with two inseminations vs. one insemination when clomiphene citrate with or without gonadotropins and 5000 IU of hCG were used. More studies are necessary to ascertain whether this is true or merely an artifact from the multiple subgroups analysis.     

Ectopic pregnancies after in vitro fertilization and embryo transfer

Objective Our objective was to analyze the risk factors, stimulation characteristics, and future fecundity of patients with ectopic pregnancies after in vitro fertilization (IVF).Methods We retrospectively evaluated all cases of ectopic pregnancy occurring between January 1989 and March 1993 (Cornell series 1 to 17). A case-control group of intrauterine pregnancies was used for comparison of the stimulation and transfer characteristics.Results Twenty-seven of 1123 pregnancies (2.4%) were ectopic, following 2812 fresh IVF embryo transfers, while 8 of 105 pregnancies (7.6%) were ectopic, following 405 frozen-thawed embryo transfers. Tubal factor was the cause of infertility in the majority (85.7%) of ectopic pregnancies. No difference was found between the ectopics and the matched controls in stimulation and transfer characteristics. Thirty ectopic pregnancies were ampullary, two were interstitial, two were cervical, and one was heterotopic. Twenty of the patients subsequently underwent 29 IVF attempts, with a pregnancy rate of 41.4% per transfer.Conclusions Ectopic pregnancy after IVF appears to be related to preexisting tubal pathology; embryo transfer of cryopreserved thawed embryos in a natural cycle may result in a higher ectopic rate in these patients; in subsequent IVF cycles the intrauterine pregnancy rate of these patients is not decreased.     

Life table analysis of intrauterine insemination pregnancy rates

One hundred twenty-eight couples undergoing intrauterine inseminations were retrospectively reviewed. Life table methodology was used to analyze cumulative pregnancy rates and monthly fecundability. Respective 6- and 12-month cumulative pregnancy rates for each diagnostic group receiving intrauterine insemination were: cervical factor, 28.6% and 42.8%; male factor, 16.7% and 16.7%; female immune factor, 66.7% and 100.0%; male immune factor, 37.5% and 68.8%; and empiric treatment, 60.0% and 60.0%. There was no difference in pregnancy rates between sperm processed with a swim-up in Ham's F-10 or a two-gradient Percoll system. Abnormal sperm penetration assay results in patients with male factor did significantly (p = 0.05) lower the pregnancy rate. It is concluded that if no pregnancy has occurred after six cycles of inseminations, further workup or other treatment may be initiated, but additional pregnancies can be achieved from the seventh through the twelfth cycles of intrauterine insemination.     

Optimization of artificial inseminations with donor semen: a four-year experience

OBJECTIVE: 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. PATIENTS AND METHODS: Retrospective analysis of the results of 249 cycles performed in 106 couples during a four-year period is reported. RESULTS: 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). DISCUSSION AND CONCLUSION: 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.     

Artificial insemination with fresh donor semen

One hundred and thirty-four patients received artificial insemination with fresh donor semen (AID). Using the life-table method of analysis, 72 pregnancies occurred, yielding a crude conception rate of 53.7%. The 134 women received an average of three inseminations per cycle for a total of 1,282 inseminations near the day of ovulation. The majority of pregnancies occurred by the seventh cycle. Forty-two pregnancies were achieved using a single donor; 30 pregnancies required changing the donor once, twice, or more. Among 42 patients who subsequently were treated with clomiphene citrate, 16 conceived. Two of these patients became pregnant after receiving hMG and hCG additionally. The life-table analysis of cumulative pregnancy rates following infertility therapy provides a relatively simple, powerful, and reliable tool for evaluating the effectiveness of therapy and its benefits. Patients should be advised that their chances of conception with AID approach that of normal fertile couples, provided that these patients persist in their treatment.     

Can donor insemination be optimised?

OBJECTIVE: To compare the different donor insemination technics. MATERIAL AND METHOD: Analysis of the published studies about donor insemination which value the effectiveness of Intra Cervical Insemination (ICID) and Intra Uterine Insemination (IUID), the interest of ovulation induction, the possible complications, and the cost-effectiveness ratio. RESULTS: The meta-analysis of the Cochrane data base (10 comparative studies IUID versus ICID, 2568 donor insemination cycles) lead to a pregnancy rate per cycle (PRC) 17.77% with IUID versus 7.68% with ICID. The odds ratio is 2.63 (CI from 1.85 to 3.73). With these PRC, the direct cost per evolutive pregnancy is 54,780 F with ICID and 25,675 F with IUID. CONCLUSION: If it is possible to propose ICID to patient with an excellent regularity of ovulation. IUID with ovulation induction by gonadotropins is today the gold standard, and more especially as the law restrict the number of donor inseminations. Indeed, the IUID is two or three times more effective than ICID, consume the half of sperm straws, use a semen of moderate quality, there is no complication provided that the cycle is cancelled if there is more than two mature follicles and the cost-effectiveness ratio is greatly in favour with IUID.     

In vitro fertilization using cryopreserved donor semen in cases where both partners are infertile

The incidence of pregnancy after in vitro fertilization (IVF) was studied in a group of 38 couples (55 cycles) where both partners were infertile. Cryopreserved donor semen (IVF-D) was used in all cycles. Results were compared with those in a control group of couples where the husband's semen was considered normal and only the wife was infertile. No significant differences were found between the IVF-D and control groups in the incidence of fertilization (80% versus 72%), pregnancy per cycle (33% versus 29%), and abortion (18% versus 20%), despite the considerably lower percentage of motile spermatozoa in the IVF-D group. Forty percent of patients, each treated unsuccessfully with at least 12 artificial inseminations with donor semen, became pregnant after one or two IVF-D cycles. It is concluded that IVF with frozen donor semen is a beneficial treatment for couples where both partners are infertile.     

Addition of gonadotrophin-releasing hormone agonist and/or two inseminations with husband's sperm do not improve the pregnancy rate in superovulated cycles

BACKGROUND: A prospective randomized study was performed to evaluate the addition of a gonadotropin releasing hormone agonist (GnRH-a) during treatment with human menopausal gonadotropins (hMG) in cycles with artificial inseminations with husband's washed sperm (AIH). We also compared the pregnancy rate per cycle after one versus two AIHs. METHODS: We designed a 22 factorial trial. A total of 172 couples with unexplained infertility (n=88), endometriosis (n=39), or cervical (n=24) or male (n=21) factors were included, of whom 161 fulfilled the inclusion criteria and treatment. Eighty-one women were treated with GnRH-a/hMG and another 80 with hMG only, respectively. RESULTS: The pregnancy rates did not differ between the two stimulation protocols (12% for GnRH-a/hMG and 9% for hMG). With GnRH-a/hMG more follicles >15 mm (3.4 and 2.4, respectively; p<0.01) and a higher multiple pregnancy rate after 20 weeks of gestation were observed (55% vs. 0%; p<0.05). Eighty-seven women were treated with one AIH, whereas 65 women received two AIHs on two consecutive days. The pregnancy rates were similar in these two groups (11% and 9% respectively; n.s.) CONCLUSION: It is concluded that neither addition of GnRH-a before and during controlled ovarian hyperstimulation nor two AIHs compared with one single AIH per cycle has a beneficial effect on the pregnancy rate. However, GnRH-a increases the risk for multiple pregnancies.     

The impact of the total motile sperm count on the success of intrauterine insemination with husband's spermatozoa

Purpose: The purpose of this study was to evaluate the relationship between the total motile sperm count and the success of IUI treatment cycles with postwashed husband spermatozoa in couples with infertility in a large patient population. Patients: When 939 couples underwent 1375 cycles of IUI with varying etiologies of infertility which included male factor, endometriosis, tubal factor, ovulatory dysfunction, uterine factor, cervical factor, and unexplained infertility, the results were 207 pregnancies. Results: The overall pregnancy rate per cycle was 15.1% (207/1375). The total motile sperm count were significantly increased in the pregnant group than the nonpregnant group (38.7×10⁶ versus 28.6 × 10⁶;P<0.001). There was a trend toward an increased success rate with increased total motile sperm count. Significance was reached when the total motile sperm count exceeded 5×10⁶. Life table analysis was performed and the curve representing a cumulative chance of pregnancy calculated from our data reached 72%. Conclusions: Our findings suggest that a final postwashed total motile sperm count used for IUI may be considered predictive of the success for pregnancy and allow couples to be informed of the chances of success.     

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source

PurposeThe aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation.MethodsWe performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed.ResultsThere were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%).ConclusionsThe use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.     

Severe oligoasthenoteratozoospermias,secretory and obstructive azoospermias: Motility as a criterion of sperm viability

Purpose: Comparison of pregnancy rates in cases of Secretory Azoospermias (SA), Obstructive Azoospermias (OA) and severe Oligoasthenoteratozoospermias (OATZ). Evaluation of sperm motility as a quality criterion. Methods: In SA cases (n = 35), 9 samples were cryopreserved. In OA cases (epididymal aspiration: n = 91; testicular biopsy: n = 206), all samples were cryopreserved. 596 OATZ ejaculates were included. Results: In SA cases, 2 pregnancies were achieved from 9 ICSI cycles. In OA, motile sperm rates were higher in testicular biopsies. After thawing sperm motility was not different between testicular and epididymal origin. 2 pregnancies were achieved with immotile testicular sperm after thawing, but none with immotile epididymal sperm. In OATZ cases, one pregnancy was obtained from the 9 cryopreserved ejaculates and 35.3% with fresh motile sperm. Conclusions: In SA cases, the use of donor sperm is recommended due to the lower pregnancy rate achieved. Motility, before and after cryopreservation, as a criterion of sperm viability is discussed and its use should be reconsidered in some cases.     

Artificial insemination: a comparison of pregnancy rates with intrauterine versus cervical insemination and washed sperm versus serum swim-up sperm preparations

A four-cycle artificial insemination protocol was undertaken, with luteinizing hormone (LH) timing, to compare washed sperm and serum swim-up sperm preparations and cervical and intrauterine insemination. Of the 75 patients entered into the protocol series, 63 finished all 4 cycles. During the treatment period, 24 patients became pregnant, 20 of whom were donor (AID) pregnancies (out of 52 patients) and 4 were husband (AIH) pregnancies (out of 11 patients). Seventy-five percent of the pregnancies were intrauterine, whereas only 25% were from cervical inseminations. Sixty-two percent of the pregnancies were due to serum swim-up sperm preparations, and 38% were due to washed sperm preparations. The data indicate substantially higher pregnancy rates can be obtained with intrauterine insemination and suggest that additional studies are necessary to determine if the method of sperm preparation significantly influences pregnancy rates.     

Retrograde ejaculation: successful treatment with artificial insemination.

Retrograde ejaculation is characterized by aspermia or oligospermia and results from an incompetent bladder neck, often due to a dysfunction of the internal sphincter. In almost 3 years, eight couples who suffered from infertility due to retrograde ejaculation were treated with inseminations with spermatozoa gained from the urine. Ovulation was predicted on the basis of blood LH levels. The urine-semen sample was collected in 100 mL of Hepes medium and 5 mL 1% human albumin (pH 7.4). After centrifuging, the remaining sperm pellet was dispersed on a Percoll gradient. After centrifuging and resuspending, followed by two washing procedures with Ham's F-10 and human albumin 1%, the remaining sample was used for intrauterine insemination. Twelve pregnancies were thus achieved; two women became pregnant twice and one three times. The pregnancy rate per cycle was 44.4%. In seven couples, pregnancy was achieved within three cycles. Four pregnancies ended in spontaneous abortion and five ended in the birth of a healthy child; three pregnancies were continuing at the time of writing. Retrograde ejaculation can be treated successfully with inseminations using spermatozoa obtained from urine. It seems important to collect the urine-semen sample in a buffered medium and to time the insemination on the basis of the LH surge.