Microsurgical testicular sperm extraction for testicular failure: the South African experience and first successful pregnancy.

BACKGROUND: In men with non-obstructive azoospermia (NOA), biological fatherhood is only possibly by specialised microsurgical sperm retrieval techniques (micro-TESE), only recently introduced to South Africa. This study aimed to analyse the spectrum of causes of NOA and the outcomes of micro-TESE, including live births, following the use of this technique in South Africa. METHODS: This was a retrospective review of all micro-TESE cases performed in South Africa by a single surgeon from 2014 to 2018. Data collected prospectively included: patient demographics, preoperative blood results, cause of azoospermia, intraoperative findings and postoperative complications. The primary outcome measured was surgical success of micro-TESE, which was defined as testicular sperm successfully retrieved and cryopreserved. Subsequent live births from assisted reproductive technology (ART) using the cryopreserved sperm were also documented. RESULTS: Twenty-six men with NOA underwent micro-TESE between May 2014 and April 2018. Mean preoperative total testosterone level was 12.0 nmol/l (IQR 5.2) and follicle-stimulating hormone level 23.5 IU/l (IQR 15.6). Genetic testing was performed as part of the preoperative work-up in only 10 of the 26 patients. A specific cause of NOA was identified in 9 of the 26 patients and included Klinefelter syndrome (1 patient), Y-chromosome AZFc microdeletion (1 patient), undescended testicles (5 patients) and chemotherapy (2 patients). The average testicular volume was 9.05 ml (IQR 5.6), and the mean duration of surgery 95.8 minutes (IQR 28.0). The overall sperm retrieval rate was 34.6%. A single pregnancy and subsequent live birth were recorded from a total of eight cycles of intracytoplasmic sperm injection (ICSI): four female partners had one ICSI cycle each and two females underwent two cycles each. Frozen and thawed sperm was used in seven of the ICSI cycles and fresh sperm in one cycle. CONCLUSION: In this South African series, sperm retrieval rates of micro-TESE for non-obstructive azoospermia were comparable to those reported internationally. Preoperative genetic testing should be increased to optimise the selection of surgical candidates.

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.

Is metformin indicated as primary ovulation induction agent in women with PCOS? A systematic review and meta-analysis.

BACKGROUND: A recent meta-analysis has proven that metformin (M) is highly effective for ovulation induction in the clomiphene citrate (CC)-resistant patient. There is uncertainty whether M should be introduced as a primary ovulation induction agent in polycystic ovarian syndrome (PCOS). METHODS: We conducted a systematic review and meta-analysis to establish if M is better when given alone or in combination with CC (CC+M) when compared with CC alone. This systematic review studied live birth delivery rate as the primary outcome. RESULTS: We identified 14 prospective trials. Analysis of these results showed a reduction in the live birth rate in the group of patients treated only with M when compared with CC alone (OR = 0.48, 95% CI 0.31-0.73, p = 0.0006). An increase in ovulation (OR = 1.6, 95% CI 1.2-2.1, p = 0.0009) and pregnancy rate (OR = 1.3, 95% CI 1.0-1.6, p = 0.05) with CC+M when compared with CC alone was reported, but no difference was found when live birth rate was analyzed (OR = 1.1, 95% CI 0.8-1.5, p = 0.61). CONCLUSION: CC alone is superior to M alone regarding live birth rate and ovulation. The combination (CC+M) is superior to CC alone as a primary method for ovulation induction and to achieve pregnancy in PCOS. However, when addressing live birth rate, no statistically significant difference could be demonstrated. Because of the side effects profile and contraindications of M, we believe M should not be indicated as a primary ovulation induction agent in women with PCOS.

Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients.

OBJECTIVE: To evaluate the benefit of Metformin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients. DESIGN: Prospective randomised controlled study. SETTING: Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town. PATIENTS: 107 patients presenting with PCOS. STUDY: Group A was pre-treated with metformin 850 mg twice a day for at least 6 weeks before clomiphene was added and the metformin was used throughout the study period. Group B received clomiphene without pre-treatment with metformin. In both groups clomiphene was given at a starting dose of 50 mg day 4-8 and increase with increments of 50 mg to a maximum of 150 mg if no response was achieved. RESULTS: The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) - C/C) is 0% with 95% confidence interval of -18.1% to 18%. The per protocol ovulation results were 34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The ovulation rate difference was 6% with 95% confidence interval -11% to 22%. In a comparison of successful ovulating versus non-ovulating women from the trial the following were significant baseline determinants: lower median weight in the ovulating group (77 kg versus 86 kg, p = .021), lower median bmi (29.0 versus 32.9, p = .009), lower median DHEAS at baseline (4.6 compared to 7.0, p = .049), lower median 17OH-progesterone (2.2 versus 4.6, p = .027) and higher baseline median SHBG ( 37.8 compared to 28.5, p = .036). CONCLUSION: Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria.

Proximal renal tubular acidosis in pregnancy. A case report and literature review.

Renal tubular acidosis is usually associated with chronic renal conditions and is rarely encountered in pregnancy. It may be inherited causing osteomalacia and rickets in children or acquired following autoimmune diseases or following exposure to nephrotoxic agents. It is known to worsen during pregnancy and if left untreated may cause maternal and foetal morbidity or death. We report a 28-year-old woman, gravida 3 para 2, who presented at 30 weeks gestation with lethargy, weakness and generalized myalgia. Investigation revealed severe hypokalaemia and a systemic metabolic acidosis due to proximal renal tubular acidosis. Her previous pregnancies were both complicated by foetal losses at term. Following prompt correction of her electrolyte disturbance and metabolic acidosis, she went on to deliver a healthy female infant at term. Regular evaluation up to 1 year post-partum revealed mild persistence of her hypokalaemia. At 1 year, the infant showed no signs of the disorder and is growing normally.

Postmenopausal bleeding: a diagnostic approach for both private and public sectors.

OBJECTIVE: To assess the optimal diagnostic approach to women with postmenopausal bleeding by comparing transvaginal ultrasound and endometrial sampling with office hysteroscopy. METHODS: A prospective collective study was performed on 102 consecutive patients with postmenopausal bleeding who were evaluated by ultrasound measurement of the endometrial thickness (EL), endometrial sampling by Accurette and outpatient hysteroscopy and directed biopsy. RESULTS: Accurette was inadequate for histological diagnosis in 65 of 136 samples and many repeat investigations were required. In all 16 cases of endometrial polyps, ultrasound measurement of the EL was > or =4 mm and hysteroscopy confirmed the findings. Accurette detected only 5 polyps. All 7 cases of endometrial hyperplasia were detected using an EL of > or =4 mm and hysteroscopy confirmed the findings. Accurette failed to detect 5 out of 7 cases of endometrial hyperplasia. Five cases of endometrial cancer were diagnosed: all had an EL > or =4 mm but were inadequately sampled for diagnostic purposes in 3 cases. A definitive diagnosis was made on hysteroscopy in 4 cases (1 patient did not have a hysteroscopy). CONCLUSION: Accurette is not a good sampling device for the diagnosis of postmenopausal bleeding. An ultrasound measurement of the EL > or =4 mm in patients with postmenopausal bleeding warrants further investigation. Outpatient office hysteroscopy is an accurate and sensitive modality to employ as a first line investigation for definitive diagnosis.

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.

A continuous quality control program for strict sperm morphology.

OBJECTIVE: To develop a training program with intervals of continuous quality control assessments for the evaluation of strict sperm morphology. DESIGN: Prospective analytical study. SETTING: Academic hospital and academic institution setting. PATIENT(S): Healthy sperm donors. INTERVENTION(S): Nine individual andrology laboratories in Switzerland were invited to participate in a training course for strict sperm morphology, which was followed up every 3 months by a continuous quality control program. Each laboratory received six slides over a period of 9 months, during which time the results were forwarded to the reference laboratory. Papanicolaou stain sperm slides were prepared and shipped to participating laboratories every 3 months. MAIN OUTCOME MEASURE(S): Percentage of normal spermatozoa. RESULT(S): The mean (+/-SE) percentage of normal sperm reported by the reference laboratory compared with the participating laboratories for slides 1-6 were 11. 4 +/- 1.6 vs. 17.3 +/- 6 (P>.2), 6.0 +/- 1.3 vs. 8.6 +/- 2.5 (P>.2), 9.0 +/- 0 vs. 9.6 +/- 3 (P>.2), 1 +/- 0 vs. 1.2 +/- 0.2 (P>.2), 23.3 +/- 0.3 vs. 28.0 +/- 1.3 (P>.2), and 2.0 +/- 0 vs. 6.1 +/- 1.2 (P>.2), respectively. Technician proficiency was reported to differ by <10% from the reference laboratory in 94% of cases. CONCLUSION(S): The results illustrate that training and proficiency testing can be conducted on a national and international level with the support of a reference laboratory. Global quality control measurements in andrology laboratories should become mandatory, since these results indicate that continuous quality control for laboratory technicians can be successful.

Surrogate pregnancies in patients with Mayer-Rokitansky-Kustner-Hauser syndrome and severe teratozoospermia.

The challenge of the case presented was threefold: congenital absent uterus (Mayer-Rokitansky-KustnerHauser syndrome), a request for surrogacy, and teratozoospermia in the husband (6% normal morphology according to the Tygerberg strict criteria). Surrogacy was dealt with by means of guidelines proposed by the SA Law Commission after a surrogate mother was found. The gestational carrier was synchronized with the genetic donor with congenital absent uterus, the main aim being assisted reproduction. Two gamete intrafallopian transfer (GIFT) procedures were performed, both unsuccessful. Poor fertilization of excess GIFT oocytes was also observed. Three intracytoplasmic sperm injection procedures were then performed. The first two were unsuccessful and the third ensued in a singleton pregnancy. Hormonal support (progesterone and estradiol valerate until 12 weeks pregnancy duration) was given. The pregnancy resulted in the normal delivery of a healthy male infant at full term. Psychological support was given to mother and surrogate throughout pregnancy, as well as thereafter. The success of this case gives hope to infertile couples with severe infertility factors.

Comparison of two staining and evaluation methods used for computerized human sperm morphology evaluations.

The purpose of the study was to analyse the agreement between computer analysed (Hamilton Thorne, IVOS Dimensions Version 3) normal sperm morphology and values obtained from 97 slides stained according to the Papanicolaou and Diff-Quik method. Liquefied semen samples were washed once by centrifugation and air dried smears on slides were made, which were stained according to the Papanicolaou and Diff-Quik method and analysed by computer. The paired t-test was used to assess whether any bias existed between the two methods. The limits of agreement were calculated using the Bland and Altman approach and a modification of this approach (mean-dependent limits). A significant bias of 1.6% was obtained in favour of higher normal sperm morphology percentages when using the Diff-Quik method. The standard limits of agreement were -13.4% to 16.6%, whereas the mean-dependent limits of agreement were 1.6% [5.8 + 0.6 (mean percentage normal morphology)]. Statistically, the Diff-Quik and Papanicolaou staining methods produce different normal sperm morphology profiles. These inherent differences may, therefore, require the establishment of new normal sperm morphology thresholds for male fertility, based on clinical data, when using the Diff-Quik staining method in conjunction with computerized analysis.

Effects of different staining and washing procedures on the results of human sperm morphology evaluation by manual and computerised methods.

The purpose of this study was to investigate the effect of different staining and washing procedures on the results of human sperm morphology evaluation by manual and computerised methods. Furthermore, it was intended to find the staining and washing combination which would provide optimal readability for computer-assisted sperm morphology evaluations. In phase one, four staining methods were evaluated for smears prepared from the resulting samples following a two times washing procedure. In phase two, 20 semen samples were used to compare the Diff-Quik and Papanicolaou staining methods, following one and two washes. All manual readings, of Papanicolaou and Diff-Quik stained smears, were comparable with each other, with means between 7.3% and 7.9% normal spermatozoa. All the manual readings were also comparable to the computer readings of the Diff-Quik slides following one and two washes with means of 9.0% and 5.9%, respectively. However, due to the higher computer readings found for the Papanicolaou stained smears, with means of 13.9% and 13.5% following one and two washes, respectively, a statistically significantly difference between overall computer and manual readings was found (Wilks' Lamda, P = 0.0002). Taking all data into consideration, it could be concluded that the one wash Diff-Quik stained smears was the optimal preparation method for computerised sperm morphology evaluation, comparing favourably with manual evaluations.

Comparison of motility characteristics and normal sperm morphology of human semen samples separated by percoll density gradient centrifugation.

The aim of this study was twofold: to investigate the ability of Percoll gradient centrifugation (52, 68, 84%) to fractionate semen samples according to motility quality and percentage normal morphology and to determine whether there is an association between sperm motility quality and percentage normal morphology. Sperm motility was evaluated using a Hamilton Thorn analyzer and normal sperm morphology was manually assessed according to the strict criteria (< or = 4, 5-14, and >14%). The majority of motility parameters and the percentage normal morphology were found to be significantly improved in the 84% Percoll fraction. The greatest effect was on the < or = 4% group, shifting the mean normal morphology percentage from 2.6 to 5.2%. Curvilinear velocity (VCL) and average path velocity (VAP) were the only two motility parameters that were significantly associated with the percentage normal morphology. Using a combined VCL, VAP vector the >14% group was found to have a significantly different value as compared to the 5-14 and < or = 4% groups. Percoll (discontinuous) gradient centrifugation can therefore play a significant role in the improvement of semen samples for use in assisted reproduction procedures. The VCL, VAP vector identified may also serve as an additional tool in the prediction of the fertility potential of sperm samples.

The influence of a mineral oil overlay on the zona pellucida binding potential of human spermatozoa.

The objective of the study was to evaluate the effect of mineral oil on zona pellucida binding potential of human spermatozoa. The study compared zona binding using micro volume droplets under mineral oil as apposed to micro droplets in cryopreservation straws. Spermatozoa from eight proven fertile sperm donors were used. One hundred and fifty five matched hemizonae in 50 microliters, 100 microliters and 200 microliters insemination sperm droplets were co-incubated; (i) under mineral oil and (ii) 0.5 ml plastic cryopreservation straws. The results were analysed to determine the number of the zona bound spermatozoa during each experiment. Microvolumes with an oil overlay had a decrease in sperm bound per hemizona of 38% (mean +/- SD; 563 +/- 415 vs. 921 +/- 597), 51% (mean +/- SD; 392 +/- 359 vs. 800 +/- 566 sperm) and 18% (mean +/- SD; 502 +/- 369 vs. 618 +/- 445) in 200 microliters, 100 microliters and 50 microliters respectively, compared to microvolumes in cryopreservation straws. It was concluded that mineral oil may have some detrimental factors which interfere with zona binding of spermatozoa.

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.

Genital tuberculosis at Tygerberg Hospital--prevalence, clinical presentation and diagnosis.

Over a period of 30 months (1 July 1986-31 December 1988) 57 cases of genital tuberculosis were diagnosed at Tygerberg Hospital. Forty of these cases were diagnosed as a result of routine screening in 650 patients who presented with infertility and the other 17 were diagnosed in patients admitted to the gynaecological wards. The prevalence in patients presenting with infertility was 6.15%. The commonest gynaecological presenting symptom was infertility (73.7%). Dysmenorrhoea in 29.8% and deep dyspareunia in 12.3% were the only other frequently occurring gynaecological symptoms. Menstruation was normal in 50 patients (87.7%). Seven per cent of patients were postmenopausal. Abdominal symptoms were only present in 15.8%. These findings re-emphasise that genital tuberculosis is often a disease of absent or few symptoms. General, abdominal and pelvic examinations were normal in 56.1% of patients and even when clinical signs were present they were nonspecific. Menstrual fluid collection and culture proved to be the most reliable diagnostic procedure, since it was positive in 11 patients in whom premenstrual endometrial sample cultures were negative and also in 17 patients in whom histological examination of premenstrual endometrial samples for tuberculosis were negative. The possible reasons for this and its clinical importance are discussed. Other than histological examination of operation and/or biopsy specimens, special investigations proved to be of little help in the diagnosis of genital tuberculosis.

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.