Fallopian tube reanastomosis by laparotomy versus laparoscopy: a meta-analysis.

OBJECTIVE: To compare efficacy of sterilization reversals by laparotomy versus laparoscopy. DESIGN: Meta-analysis. SEARCH STRATEGY: Electronic searches were carried out for randomized controlled trials and retrospective and prospective clinical studies. Search engines such as PubMed, Science Direct, Medline and the Cochrane database were made use of. Our restrictions were English human studies published from 1989 to January 2010. INTERVENTIONS: Microsurgical tubal reanastomosis performed comparing laparoscopy with laparotomy using a microsurgical technique. OUTCOME MEASURES: Primary: overall pregnancy rates, including positive clinical pregnancy, intrauterine and ectopic pregnancy rates. Secondary: surgery time. RESULTS: Three retrospective comparative studies were retrieved from international data that investigated laparotomy versus laparoscopy. A total number of 184 patients were included, 88 and 96 respectively undergoing laparoscopy and laparotomy. Pregnancy rates achieved by laparoscopy ranged from 65 to 80.5% (mean 74.43%) and by laparotomy from 70 to 80% (mean 71.33%). A subanalysis of two of the three comparative studies show that laparoscopy reversal surgery requires a statistically significant longer operative time than does laparotomy (p < 0.00001). CONCLUSIONS: There is no difference between the laparoscopy and laparotomy approach to tubal reanastomosis when regarding overall pregnancy rates, intrauterine and ectopic pregnancy rates.

Gamete intrafallopian transfer as treatment for infertility associated with endometriosis.

Forty-six patients with endometriosis-associated infertility underwent 59 GIFT cycles. The pregnancy rate per cycle was 30.5%. The presence of endometriomas in 11 patients did not affect this rate adversely. We conclude that, provided at least one fallopian tube is patent, GIFT compensates effectively for the possible causes of infertility in these patients.

Treatment of male sperm autoimmunity by using the gamete intrafallopian transfer procedure with washed spermatozoa.

Sixteen couples were diagnosed as having immunological infertility. To detect sperm-bound immunoglobulin (Ig), i.e., IgA, IgG, and IgM antibodies, the direct immunobead test (IBT) was used. In each individual patient, the direct IBT was greater than or equal to 70% positive for either IgA or IgG or both. The indirect IBT was positive for IgA and IgG antibodies in the serum of all the patients. Semen was collected in 15 mL medium (Ham's F10 [Gibco, Grand Island, NY] + 10% whole blood serum) and prepared with the wash and swim-up method. Patients in the study group were treated for their immunological infertility problem by performing the gamete intrafallopian transfer (GIFT) procedure. An ongoing pregnancy was achieved in 7 of the 16 (43%) couples treated with the GIFT procedure with an ongoing pregnancy rate of 24.1% (7 of 29) per cycle. The GIFT procedure appears to be an effective and safe way of treating male immunological infertility.

The role of oocyte maturity in the treatment of infertility because of teratozoospermia and normozoospermia with gamete intrafallopian transfer.

OBJECTIVE: To determine the effect of oocyte maturity on pregnancy rate (PR) in patients undergoing gamete intrafallopian transfer (GIFT) procedures for infertility and in whom male partners had either normozoospermia or teratozoospermia. DESIGN: A prospective study using a combination of clomiphene citrate and human menopausal gonadotropin for ovulation induction was carried out. Five hundred thirty-seven GIFT treatment cycles were analyzed, and 423 cycles yielded four or more oocytes. Patients were divided into two groups according to the sperm morphology: those with less than 14% normal forms and those with greater than 14% normal morphology (as judged by strict criteria). These two groups were divided into a further five subcategories depending on the number of metaphase II oocytes transferred. RESULTS: In the group less than 14% normal forms (category I; 4 metaphase I oocytes replaced), three pregnancies resulted from 33 cycles (9.09%), and in category V (4 metaphase II oocytes transferred) the PR was 15% (14/95) per cycle. In the group with greater than 14% normal forms, in category I, the PR was 16% (3/19) per cycle, and in category V, the PR was 33% (20/61) per cycle. The effect of morphology (less than 14% normal forms versus greater than 14% normal forms) on pregnancy outcome is significant (P = 0.0161). The overall effect of increasing the number of metaphase II oocytes on the pregnancy outcome was not significant (P = 0.1098). However, in the group with greater than 14% normal forms, there was a significant improvement in PR (P = 0.04) in category V. CONCLUSION: During this prospective study, it was shown that sperm morphology plays a significant role in the pregnancy outcome in a GIFT program.

Fertilization efficiency of morphologically abnormal spermatozoa in assisted reproduction is further impaired by antisperm antibodies on the male partner's sperm.

OBJECTIVE: To investigate the influence of antisperm antibodies on the sperm surface on the outcome of IVF and GIFT. DESIGN: Matched controlled retrospective review of two large series. SETTING: Reproductive endocrine divisions of two level-three academic centers. PATIENTS: Twenty-nine male factor patients (38 IVF cycles) showing positive antisperm antibodies on the sperm by immunobead test treated by IVF at the Norfolk program and 56 similar patients (57 cycles) treated by GIFT at the Tygerberg program. Twenty-nine male factor patients (29 IVF cycles) with negative antisperm antibodies screening matched by wife's stimulation protocol and baseline semen analysis characteristics were used as controls in Norfolk; 56 GIFT patients (56 GIFT cycles) matched similarly were the Tygerberg controls. Study and control groups were divided according to sperm morphology pattern in normal, good, and poor prognosis subgroups for comparison. MAIN OUTCOME MEASURES: Fertilization rate of preovulatory oocytes used in IVF in Norfolk and of GIFT supernumerary preovulatory oocytes in Tygerberg; total and term pregnancy rates (PRs) and abortion rates. RESULTS: Fertilization rate was significantly lower in the IVF (41.9% +/- 2.8%) as well as in the GIFT (26.8% +/- 3.8%) (mean +/- SE) study groups than in the respective control groups (73.1% +/- 3.9% and 61.8% +/- 3.9%). Total and term PRs in IVF per cycle (21.1% +/- 6.6%; 13.2% +/- 5.5%) and per transfer (23.5% +/- 7.4%; 14.7% +/- 6.1%), and in GIFT (25.0% +/- 5.8%; 19.6% +/- 5.3%) in the study groups were also lower when compared with their control counterparts (IVF per cycle: 62.1% +/- 6.2% and 41.4% +/- 6.0%; IVF per transfer: 41.9% +/- 2.0% and 27.9% +/- 1.9%; GIFT: 31.6% +/- 6.2% and 28.1% +/- 6.0%), but the difference did not reach statistical significance. Abortion rates were similar in the IVF study group (37.5% +/- 17.1%) and its control groups (39.9% +/- 11.5%). The abortion rate in the GIFT study group was 14.3% +/- 9.4%, and no abortions were recorded in the control group (not significant). CONCLUSIONS: The presence of antisperm antibodies on the sperm surface per se impairs the outcome of assisted reproduction, mainly in terms of fertilization rate of preovulatory oocytes, and possibly in terms of total and term PRs. This holds true regardless of the impact of other semen parameters, particularly the morphology of the sperm within the semen sample.

Sperm morphologic features as a prognostic factor in in vitro fertilization.

To determine whether there is a prognostic value in the percentage normal sperm morphologic features in a human in vitro fertilization (IVF) program, the authors conducted a prospective study in women with bilateral tubal damage. Based on the percentage of morphologically normal spermatozoa, the patients were divided into four groups: group I, normal morphologic features between 0% and 14%; group II, 15% to 30%; group III, 31% to 45%; and group IV, 46% to 60%. One hundred ninety successful laparoscopic cycles were evaluated. In group I, 104 oocytes were obtained, of which 37% fertilized, but no pregnancy resulted; in group II, 81% of 324 oocytes were fertilized, with a pregnancy rate per embryo transfer (ET) of 22%; in group III, 82% of 309 oocytes were fertilized, with a 31% pregnancy rate; and in group IV, 91% of 69 oocytes were fertilized, with a pregnancy rate of 12%. Probability models indicated that there was a clear threshold in normal sperm morphologic features at 14%, with high fertilization and pregnancy rate in the groups with normal sperm morphologic features greater than 14%.

Effect of fibroids on fertility in patients undergoing assisted reproduction. A structured literature review.

OBJECTIVE: The aim of this study is to evaluate the current data to understand the impact of intramural leiomyomata on pregnancy outcome in assisted reproduction. PATIENTS AND METHODS: In this review, articles were found by means of computerized Medline and Cochrane Library search using the key words uterine myomata, leiomyomata, fibroids, implantation, pregnancy, infertility and in vitro fertilization. Limitations were English, human, 1990-2002. Inclusion criteria were pregnancy data on in vitro fertilization, intramural myomata with no cavitary distortion and control groups without myomas for each patient with a myoma. RESULTS: There was a significant negative impact on implantation rate in the intramural myomata groups versus the control groups, 16.4 vs. 27.7% OR 0.62 (0.48-0.8). The delivery rate per transfer cycle was also significantly lower (myomata vs. control), 31.2 vs. 40.9% OR 0.69 (0.50-0.95). CONCLUSION: Our study supports the notion that patients with intramural fibroids have a lower implantation rate per cycle. The studies did not shed new light on the size of intramural myomata that could affect the outcome. In previous failed in vitro fertilization cycles, microsurgical removal of myomata must be considered.

Comparative trial of clomiphene citrate/human menopausal gonadotropin and the contraceptive pill, followed by clomiphene citrate/human menopausal gonadotropin, in a gamete intrafallopian transfer program.

PURPOSE: It may sometimes be necessary to regulate cycles in assisted reproduction. Cycles can be regulated with gonadotropin releasing hormone (GnRHa) agonist but other methods can also be used. The aim of this study was to compare the pregnancy rate in a gamete intrafallopian transfer (GIFT) program in patients receiving a contraceptive pill/Clomid/human menopausal gonadotropin (hMG) regimen (study group), with the standard Clomid/hMG regime (control group). Fifty one patients in the study group were carefully matched for patient age, infertility diagnosis (female), semen parameters, number of follicles, and number of oocytes transferred into consideration with a control group. RESULTS: The overall pregnancy rate was 21.6% (11/51) in the study group and 47% (24/51) in the control group (P = 0.01). However, the ongoing pregnancy rate in the two groups did not differ significantly, 11.8% (6/51) vs 27.5% (14/51) (P = 0.08). In the study group, 7.8% of patients had to be seen over a weekend, compared to 13.7% in the control group (not significant). CONCLUSION: From the findings we conclude that, although this method of controlling cycles can be useful in selected patients, it is not the ultimate method.

A comparative study using prepared and unprepared frozen semen for donor insemination.

The aim of this study was to compare the efficacy of pericervical insemination with unprepared semen With that of intrauterine insemination with prepared donor semen in a prospective, randomized, crossover clinical trial. Fifty-four subsequent patients who qualified for therapeutic donor insemination were randomized to receive alternately either an intrauterine insemination with thawed frozen donor semen, prepared by double wash and swim-up, or pericervical insemination with unprepared thawed frozen donor semen in subsequent treatment cycles, with each patient serving as her own control. Eleven pregnancies ensued from 54 cycles of intrauterine insemination (20.4% per cycle), and 2 pregnancies ensued from 58 cycles of pericervical insemination (3.4% per cycle, p = .005). Five pregnancies ensued during the first treatment cycle (13.2%), 4 during the second treatment cycle (17.4%), 2 during the third (13.2%), 1 during the fourth (7.1%), and 1 after the fourth treatment cycle (4.8%). The significantly better pregnancy rate from intrauterine insemination with prepared semen supports this treatment option. The decrease in pregnancy rate after the fourth treatment cycle confirms the need for alternative therapy after 4 failed cycles of therapeutic donor insemination.

[Ovulation induction for in vitro fertilisation at the Tygerberg Hospital]. / Ovulasie-induksie vir in vitro-bevrugting in Tygerberg-hospitaal.

The protocol for in vitro fertilisation (IVF) at Tygerberg Hospital is presented and the results are analysed. Indications for ovulation induction for IVF included the following: (a) irreversible tubal damage; (b) infertility due to immunological factors; (c) male factor-infertility; and (d) endometriosis. A combination of human menopausal gonadotrophin (HMG) and clomiphene citrate (Clomid; Mer-National) and human chorionic gonadotrophin was used. Clomid is given in dosages of 100 mg for 5 days depending on the cycle length. Three doses of HMG (150 IU) are given on alternate days, starting on the second day of clomiphene treatment. If the leading follicle has not reached a mean diameter of 14 mm the day after the last HMG dose, another dose is given. This dosage is continued until the leading follicle reaches a diameter of 14 mm. A total of 109 cycles in 100 patients was analysed. Ova were considered to be mature as soon as the dominant follicle had reached a sonographic average diameter of 18 mm, another two follicles of 16 mm average diameter being present. Serum luteinising hormone levels were determined 4-hourly from the stage when the leading follicles exceeded an average diameter of 14 mm. In this study the pregnancy rate was 21,3% per laparoscopy and 24,4% per embryo transfer. The oestradiol levels on the 5th day of treatment have a predictive value of the length of stimulation.

[Artificial intrauterine insemination with washed prepared spermatozoa of the husband]. / Kunsmatige intraüteriene inseminasie met gewaste voorbereide eggenootsemen.

Intra-uterine insemination with washed spermatozoa of the husband was evaluated in 42 infertile couples during 103 treatment cycles. A pregnancy rate of 47.3% was obtained after an average of 2 treatment cycles in a group of patients in whom hostile cervical mucus was the only known cause of infertility. A pregnancy rate of 21.7% was obtained after an average of 2.6 treatment cycles in a group of patients in whom low sperm morphology was the only known cause of infertility. The overall conception rate of 33.3% compares favourably with that in other published series.

Severe ovarian hyperstimulation after follicular aspiration.

In order to maximise the chances of pregnancy, most successful in vitro fertilisation programmes use a combination of ovulation induction agents. This treatment can lead to the hyperstimulation syndrome. Aspiration of the follicles is believed to avoid this syndrome. Despite this approach, hyperstimulation syndrome may still develop. The clinical picture and treatment of a patient with severe hyperstimulation is discussed.

Follicle stimulating hormone levels on cycle day 3 predict ovulation stimulation response.

AIM: To determine the value of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on cycle day 3 in predicting the ovulation stimulation response in patients receiving exogenous gonadotropins for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). METHODS: One hundred eleven consecutive females with infertility due to various etiologies were investigated. Cycle day 3 serum levels of FSH, LH, and E2 were determined prior to ovulation induction with a combination of clomiphene citrate and human gonadotropins. Follicular growth was monitored ultrasonically, and when appropriate, oocytes were recruited, counted, graded, and then used, as prearranged, for either IVF or GIFT. Basal hormone levels were compared to the peak E2 concentration, the number of follicles aspirated, and the number of preovulatory oocytes recovered following drug therapy. Details of resulting pregnancies were also recorded. RESULTS: Patients with low basal FSH levels (< 11.5 mIu/ml) yielded a higher mean number of preovulatory oocytes than those with high values (> 11.5 mIu/ml), i.e., 6.7 oocytes per cycle vs 2.5 oocytes (P < 0.001). In the low group 97% of cycles yielded more than three fertilizable oocytes compared to 42% in the high group (P < 0.5). There were 16 term pregnancies (16%) in the low group and 1 (8.3%) in the high group. Basal LH and E2 levels did not improve on the ability to distinguish between different populations of infertile females who responded differently to ovulation induction. CONCLUSION: Cycle day 3 FSH levels are predictive of the ovulation response and probability of pregnancy in stimulated cycles and can be of value in patient selection and counseling in IVF and GIFT programs.

Intracytoplasmic sperm injection with testicular spermatozoa in men with azoospermia.

PURPOSE: The aim of the study was to gain an insight into the optimal management of the infertile couple with the husband suffering from azoospermia. METHODS: One hundred and forty-two intracytoplasmic sperm injection (ICSI) cycles performed with testicular extracted spermatozoa were retrospectively analysed. The following factors were investigated for their possible influence on fertilization, cleavage, damage, pregnancy, and ongoing pregnancy rates: the use of fresh, cryopreserved, and preincubated (24 h) spermatozoa and the etiology of the husbands' azoospermia (obstructive and nonobstructive). All microinjections were performed with apparently normal spermatozoa--a head with a tail of normal length. In 116 cycles at least two embryos were available for transfer. RESULTS: The overall fertilization, clinical pregnancy, and ongoing pregnancy rates obtained for the 116 cycles were 65.0, 30.2, and 22.4% respectively. Similar outcomes were obtained for cycles using fresh testicular and cryopreserved testicular spermatozoa. Similarly, no significant differences were obtained between the cycles using spermatozoa from obstructive or nonobstructive azoospermic patients. An increase in motility after a 24-h preincubation was observed, and although this group was relatively small (n = 17), a significant improvement in fertilization (73.7%) and pregnancy (53.9%) rate was obtained when the testicular sample was preincubated for 24 h. This improvement prevailed in the obstructive azoospermic group, but was less pronounced in nonobstructive patients. CONCLUSIONS: This study shows that the outcome of fresh and frozen-thawed testicular spermatozoa in ICSI is comparable, obstructive and nonobstructive etiologies perform the same, and that preincubation of testicular spermatozoa results in increased fertilization and pregnancy rates. All testicular biopsies are therefore performed the day before oocyte retrieval, superfluous spermatozoa cryopreserved, and the remaining testicular homogenate preincubated for the 24 h prior to oocyte retrieval. With this regime, most azoospermic patients are treated successfully, irrespective of the use of fresh or frozen-thawed spermatozoa from obstructive or nonobstructive cases.

Factors affecting pregnancy outcome in a gamete intrafallopian transfer (GIFT) programme.

OBJECTIVE: To identify the factors that most significantly affected pregnancy rates in a gamete intrafallopian transfer (GIFT) programme. METHODS: A total of 863 GIFT cycles were analysed retrospectively. The variables found to be associated significantly with pregnancy were then used to obtain multivariate analysis using logistical regression. RESULTS: Overall and ongoing pregnancy rates were significantly better in patients < or = 38 years than in patients > 38 years (37.3% and 28.4% v. 23.7% and 11.0% respectively), and age was positively associated with success after GIFT (odds ratio (OR) 1.87, 95% confidence interval (CI): 1.22-2.85). Metaphase I (MI) oocytes were negatively associated with pregnancy (OR 1.54, 95% CI: 0.28-1.04). The highest pregnancy rates occurred when 3 metaphase II (MII) oocytes were transferred (39.8%, OR 7.51, 95% CI: 1.74-32.42). With regard to sperm morphology, overall pregnancy rates of 25.5% (< or = 4% normal forms) and 37.2% (> 4% normal forms) were obtained. Morphology of > 4% normal forms was positively associated with pregnancy (OR 1.58, 95% CI: 1.04-2.42). CONCLUSION: The results of this study suggest that the most important factors influencing pregnancy rates in a GIFT programme are the woman's age and those factors pertaining to the characteristics of the gametes. Considering the emotional and financial costs it is important to relate this information to all prospective participants in a GIFT programme.

The technique for human embryo transfer at Tygerberg Hospital.

From 1 May 1984 to 30 April 1985 177 laparoscopies were performed; 684 oocytes were obtained and a fertilization rate of 85% per oocyte achieved. There was a pregnancy rate of 24.3% per embryo transfer (ET) and 20.9% per laparoscopy after 152 patients were subjected to ET. The ET technique at Tygerberg Hospital, using the Tomcat catheter, is described. An introducer--the FT introducer--designed to overcome technical difficulties in selected patients in passing the Tomcat catheter is described. Technical problems are easily overcome with this introducer. In 26 patients (17.1%) ET was performed using this instrument and 8 pregnancies resulted (a pregnancy rate of 30.7% per ET). This pregnancy rate indicates the value of the instrument.

Stepwise regression analysis to study male and female factors impacting on pregnancy rate in an intrauterine insemination programme.

The aim of this study was to evaluate the impact of male and female factors on the pregnancy rate in an intrauterine insemination (IUI) programme. Data on 522 cycles were retrospectively studied. All patients 39 years or younger were included in the study where data were available on male and female diagnosis, as well as on ovulation induction methodology. Regression analysis was possible on 495 cycles to study different factors affecting the pregnancy rate per treatment cycle. Logistic regression identified variables which were related to outcome and were subsequently incorporated into a statistical model. The number of follicles was found to have a linear association with the risk ratio (chance) of pregnancy. The age of the woman was also found to have a linear (negative) association with pregnancy. The percentage motility and percentage normal morphology (by strict criteria) of spermatozoa in the fresh ejaculate were the male factors that significantly and independently predicted the outcome. Percentage motility > or = 50 was associated with a risk ratio of pregnancy of 2.95 compared to percentage motility < 50. Percentage normal sperm morphology > 14% was associated with a risk ratio of pregnancy of 1.8 compared to percentage normal morphology < or = 14%. Female patients with idiopathic infertility were divided into three groups according to normal sperm morphology. The pregnancy rate per cycle was 2.63% (1/38) for the P (poor) pattern group (0-4% normal forms), 11.4% (17/149) for the G (good) pattern group (5-14%), and 24% (18/75) for the N (normal) pattern group (> 14% normal forms). A female diagnosis of endometriosis or tubal factor impacted negatively on the probability of pregnancy (risk ratio of 0.17), compared with other female diagnoses. Male and female factors contribute to pregnancy outcome, but the clinician can influence prognosis by increasing the number of follicles, especially in severe male factor cases.

The effect of serum supplementation on the cleavage of human embryos.

The effect of serum supplementation was evaluated on 108 oocytes obtained from 29 patients. The oocytes were all mature and randomly distributed in two groups. Each ovum was paired with another ovum within the same patient. The experimental group contained no serum in the insemination and growth medium, but in the control group 10% serum was added to the insemination and growth medium. In the experimental group the cleavage rate was 66.7%, compared to 83.3% in the control group. The embryos from each patient were individually evaluated. The sign test was used for statistical analysis. A significant difference between the two groups (P = 0.01) indicated that in this study the addition of serum to the medium gives better cleavage results. The effect of serum on embryos is discussed, as well as the practical implications of this finding.

Human pregnancy after transfer of intact frozen-thawed embryos.

Since the birth of the first baby as a result of in vitro fertilisation (IVF) in 1978, many clinics around the world have achieved pregnancies and births for their patients by using IVF and gamete intrafallopian transfer procedures. With the storage of excess embryos, multiple laparoscopies can be avoided; this has favoured the development of better cryopreservation techniques. In our clinic 8-cell human embryos are frozen in a 1.5M dimethyl sulphoxide solution as cryoprotectant using the slow freeze-thaw method. Sixteen thawed embryos were replaced in 8 patients, resulting in 1 pregnancy. Of the thawed embryos 51.6% survived the freezing process in that they had 50% or more of the original number of blastomeres and also the zona pellucida intact.