Andrology: Nuclear decondensation of sperm head and failure at in-vitro fertilization: an ultrastructural study

The problem of unexplained male infertility was investigatedby electron microscopic study of spermatozoa from 51 males.The subjects were subdivided as follows: group A (n = 25) normalfertile males (controls), group B (n = 13) successful in-vitrofertilization (IVF) cases (fertilization rate >50%), groupC (n = 13) failed IVF cases. All subjects included in groupsB and C had a 6–12 year history of childlessness and IVFwas employed when other methods of assisted reproduction failed.The study of spermatozoa in fertile males (controls) was carriedout to establish baseline ultrastructural abnormalities. Inall 51 cases, an average of 330 (280–800) sperm headsand 660 (330–1190) sperm tails were studied. Decondensationof nuclear chromatin was observed in 70 ± 15% (mean ±SD) of spermatozoa in failed IVF cases, 16 ± 5% in successfulIVF cases and 7 ± 3% in controls. These results werefound to be statistically significant (P > 0.001). The meanvalue for motility of spermatozoa in all three groups was withinaccepted limits of normality. It is concluded that decondensationof nuclear chromatin seen by electron microscopy is one of themost important causes of male infertility. It is advocated thatelectron microscopic examination of semen should be carriedout in all cases of longstanding, unexplained male infertilitybefore embarking upon IVF programmes.     

Endocrinology: The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization--a randomized study

A group of 78 infertile women, diagnosed as having tubal factorinfertility only, was enrolled in a prospective, randomizedstudy conducted to determine whether the addition of differentdoses of glucocorticoids to the protocol of ovulation inductionfor in-vitro fertilization (IVF) would be beneficial. Oocytenumbers, percentage of fertilization, oestradiol, luteinizinghormone and follicle stimulating hormone serum concentrations,number of embryo transfers and pregnancy rate were evaluated.Compared to control cycles (group A; n=24), the addition of0.5 mg (group B; n=27) or 1 mg dexamethasone (group C; n=27),combined with the protocol of programmed oocyte retrieval forIVF patients in the study, demonstrated equivalent results.The mean numbers of oocytes retrieved were 10.8±3.9 inthe control group, compared to 11.2±4.0 in group B and10.5±3.6 in group C. The fertilization rates were 69±21,66±18 and 70±15% respectively. The pregnancy rateswere 20, 16 and 20.8% respectively. The addition of up to 1mg dexamethasone daily to the protocol of ovulation inductionfor oocyte retrieval did not improve the overall IVF-embryotransfer outcome in patients with tubal factor infertility.     

Endocrinology: Predictive value of serum oestradiol concentrations and oocyte number in severe ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a serious complicationof gonadotrophin usage but it is difficult to accurately predictits occurrence. Previous investigators have identified the combinationof high oestradiol concentrations and oocyte number as beingpredictive in 80% of cases. In this study we sought to identifythe incidence of severe OHSS in patients with high oestradiolconcentrations and large numbers of oocytes and to evaluatethe importance of pregnancy in the development of OHSS. Between1990 and 1993, we studied 139 cycles using two assisted reproductivetechniques [oocyte donor, n =72; in-vitro fertilization (IVF),n = 67] in which either oestradiol (>4000 pg/ml), oocytenumber (>25), or both were elevated. OHSS was diagnosed bystandard criteria. There were no cases of severe OHSS in theoocyte donor group and six in the IVF group. Among 10 patientswith oestradiol concentration >6000 pg/ml and >30 oocytes,only one had OHSS (10%). The relative risk of OHSS with pregnancywas 12 (confidence interval 2.18–66.14). We conclude thatthe risk of OHSS even at high levels of stimulation is lowerthan previously believed. Secondly, donors have a very low riskof OHSS, probably because of the absence of pregnancy. As such,cryopreservation of all oocytes in IVF cycles is a reasonablealternative to cycle cancellation or use of adjunctive medication.     

A combination of norethindrone acetate and leuprolide acetate blocks the gonadotrophin-releasing hormone agonistic response and minimizes cyst formation during ovarian stimulation

A protocol utilizing both leuprolide acetate (LA) and norethindroneacetate (NETA) in subjects undergoing ovarian suppression priorto follicle aspiration proved more effective than LA alone inreducing the incidence of ovarian cyst formation without affectingclinical outcome. Patients (n = 105) undergoing ovarian stimulationfollowed by follicle aspiration and in-vitro fertilization (IVF)were prospectively randomized and studied. Study measures includedovarian suppression days, days of human meno-pausal gonadotrophin(HMG) stimulation, serum oestradiol concentrations, number ofcycles developing de novo cysts (>15 mm), number of inducedflare responses (day 8 oestradiol 5=50 pg/ml), number of officevisits, total dose exogenous gonadotrophins, number oocytesretrieved, and clinical pregnancy and delivery rates per retrieval.Patients undergoing FVF received either LA alone (n = 58; controls)or LA and NETA (n = 47; study group) for the first 8 days oftheir cycle. Results comparing NETA/LA versus LA demonstrated:serum oestradiol 20.7 ± 3.9 versus 573 ± 9.4 pg/mlrespectively on day 8 of ovarian suppression (P < 0.01);8.6 ± 2.74 days required for ovarian suppression versus123 ± 6.09 days (P < 0.01); and only three individuals(6.4%) using NETA/LA developed ovarian cysts >15 mm comparedto 15 (25.9%) controls (P < 0.01). No differences were observedfor days of stimulation, peak oestradiol attained, total dosageof exogenous gonadotrophins, or number of aspirated oocytes.Neither were there differences in the clinical pregnancy (26.8versus 22.6%) nor in delivery rates (19.5 versus 20.8%). Weconclude that the addition of NETA to LA enhances ovarian suppressionand lessens ovarian cyst formation, thereby significantly decreasingthe overall cost per cycle.     

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome

Total ovarian volumes were measured before the administrationof HCG in 42 women undergoing treatment for infertility by in-vitrofertilization (IVF) and embryo transfer and considered to havean exaggerated response to stimulation (>20 follicles). Sevenwomen who subsequently developed moderate or severe ovarianhyperstimulation syndrome (OHSS) (n = 7; group 1) were comparedwith 35 matched controls (five matched controls per case; n= 35; group 2) of similar age, number of follicles and durationof infertility who underwent follicular stimulation, oocyterecovery, in-vitro fertilization and embryo transfer duringthe same period but did not develop moderate or severe OHSS.The mean age, duration of infertility and total number of follicleswere similar but the mean total ovarian volume was significantlyhigher in the group of women who developed moderate or severeOHSS compared with controls (271.00 ± 87.00 versus 157.30± 54.20 ml; P < 0.01). We conclude that total ovarianvolume measured before HCG administration is higher in womenwho develop moderate or severe OHSS compared with controls andmay therefore be used as an additional parameter in the preventativestrategy for the ovarian hyperstimulation syndrome.     

Association of early {beta}-human chorionic gonadotrophin values with pregnancy wastage and multiple implantation in a donor oocyte programme

An early marker predictive of a viable pregnancy would easethe anxiety associated with positive pregnancy tests after theuse of donor oocytes. We examined the predictive value of anearly serum quantitative human chorionic gonadotrophin (Q-HCG)concentration on pregnancy outcome following oocyte donation.Embryo transfers after oocyte donation resulting in a positiveserum -HCG were examined beginning 9 days after embryo transferfrom those samples assayed in our laboratory (n = 77). Q-HCGconcentrations were measured in our laboratory by an immunoradiometricassay utilizing the first International Reference Preparation.Implantations were defined as the number of gestational sacsvisualized by transvaginal ultrasound 21 days after embryo transfer.Biochemical pregnancies were those with transient elevationsin -HCG concentration but without implantation sites. Spontaneousabortions were characterized by an implantation site with theeventual arrest of development. Ongoing/delivered pregnanciesdeveloped appropriately and proceeded beyond the first trimester.Day 9 Q-HCG concentrations did not differentiate between biochemicalpregnancies/spontaneous abortions and ongoing/delivered pregnancies,although mean ± SD concentrations for biochemical pregnancieswere significantly lower than those for the other groups (P< 0.0001): biochemical pregnancies, n = 18, 5.8 ±8.9 mlU/ml, range 0–35; spontaneous abortions, n = 2,46.0 ± 10.0 mlU/ml, range 39–53; ongoing/deliveredpregnancies, n = 57, 41.5 ± 35.4 mlU/ml, range 0–214.In addition, day 9 Q-HCG concentrations did not differentiatebetween multiple implantations, although the implantation offour sacs had a significantly higher mean Q-HCG concentrationcompared with the implantation of fewer sacs (P > 0.0001):one sac, n = 22, 32.2 ± 21.5 mlU/ml, range 3–78;two sacs, n = 25, 35.8 ± 21.3, range 0–81; threesacs, n = 7, 47.1 ± 37.1 mlU/ml, range 22–126;four sacs, n = 4, 122.3 ± 62.4 mlU/ml, range 76–214.The positive predictive value of a Q-HCG >10 mlU/ml was 0.91(sensitivity 91%, specificity 75%). These initial data suggestthat early day 9 serum Q-HCG determinations do not accuratelyidentify viable pregnancies or multiple implantations. Evenan early negative pregnancy test should be repeated becauseit can be associated with a normal pregnancy.     

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization*

The adverse effect of raised luteinizing hormone (LH) concentrationson reproductive outcome suggests that exogenous LH administrationfor ovarian stimulation may not be desirable. The aim of thisstudy was to compare the clinical pregnancy rates between folliclestimulating hormone (FSH) and human menopausal gonadotrophin(HMG) used in in-vitro fertilization (IVF) cycles. A total of232 infertile patients, with a mean duration of infertilityof 67.1 ± 32.9 months, were selected for IVF (femaleage <38 years, FSH <15 IU/1, and total motile sperm count>5x10⁶). A short (flare-up) protocol with daily leuprolideacetate was followed randomly from day 3 with FSH (n = 115)or human menopausal gonadotrophin (HMG; n = 117), at an initialdose of two ampoules per day. A maximum of three embryos wastransferred, and the luteal phase was supported with four dosesof HCG (2500 IU). No differences were observed between the twogroups in any of the cycle response variables except fertilizationrates per oocyte and per patient, both of which were significantlyhigher with FSH. Clinical pregnancy rates per cycle initiated,per oocyte retrieval and per embryo transfer were 19.1, 21.0and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectivelyfor HMG. Whilst these differences were not statistically significant,the results of this interim analysis suggest that HMG may beassociated with a lower clinical pregnancy rate than FSH.     

Andrology: A new predictive test for in-vitro fertilization based on the induction of sperm acrosome reaction by N-acetylglucosamine-neoglycoprotein

Neoglycoproteins with N-acetylglucosamine residues (BSA-GIcNAc)induced specifically the acrosome reaction (AR) in human spermatozoa.Our objective was to investigate the relationship between thisphenomenon and the in-vitro fertilization (IVF) rate. Spermsuspensions from IVF protocols were incubated with BSA-GlcNAc(t), using calcium ionophore (i) or medium alone (c) as positiveor negative controls. When the normalized AR percentage ratio(STIM) (%ARt-%ARc): (%ARi-%ARc) was compared with fertilizationrate in 31 couples from our IVF programme, a positive correlationwas found (r = 0.46, P < 0.01). The fertilization rate inpatients with STIM 0.2 was higher than in non-responders (STIM< 0.2); 72 ± 7% compared with 5 ± 3%. The overallpredictive value of this test for adequate fertilization rate(>30%) was 87%, sensitivity 91% and specificity 78%. Falsepositives were 9% and false negatives 22%. For successful fertilizationrates (>60%), the results were: overall predictive value,84%; sensitivity 100%; specificity 64%. False positives were23% and no false negatives were found. The results indicatedthat the induction of AR in human spermatozoa by GlcNAc-neoglycoproteinscould be used to predict their fertilizing ability in vitro.     

Pregnancy: Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advancedreproductive age (45 years old) and followed their pregnanciesthrough to delivery in order to assess obstetrical outcomes.Patients (n = 162) aged 45–59 years (mean ± SD;47.3 ± 3.4 years) underwent 218 consecutive attemptsto achieve pregnancy. Oocytes (16.2 ± 7.2 per retrieval)were provided by donors 35 years old. Cleaving embryos (8.2± 4.8 zygotes/couple) were transferred trans-cervically(4.5 ± 1.1 per embryo transfer) to recipients prescribedoral micronized oestradiol and intramuscular progesterone. Followingoocyte aspiration there were six instances of non-fertilization(2.8%) and 212 embryo transfers. A total of 103 pregnancieswas established for an overall pregnancy rate (PR) of 48.6%,which included 17 preclinical pregnancies, 12 spontaneous abortions,and 74 delivered pregnancies (clinical PR 40.6%; delivered PR34.9%). Multiple gestations were frequent (n = 29; 39.2% ofpregnancies) and included 20 twins, seven triplets, and twoquadruplets. Two of the triplet and both of the quadruplet pregnanciesunderwent selective reduction to twins. Antenatal complicationsoccurred in 28 women (37.8% of deliveries) and included pretermlabour (n = 9), gestational hypertension (n = 8), gestationaldiabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia(n = 2), HELLP syndrome (n = 2), and fetal growth retardation(n = 2). 48 (64.8%) deliveries were by Caesa-rean section. Thegestational age at delivery for singletons was 383 ±1.3 weeks (range 35–41 weeks), with birth weight 3218± 513 g (range 1870–4775 g); twins 35.9 ±2.0 weeks (range 32–39 weeks), birth weight 2558 ±497 g (range 1700-3450 g); and triplets 33.5 ± 0.7 weeks(range 32-34 weeks), birth weight 1775 ± 190 g (range1550-2100 g). Neonatal complications (4.6% of babies born) includedgrowth retardation (n = 2), trisomy 21 (n = 1), ventricularseptal defect (n = 1), and small bowel obstruction (n = 1).There were no maternal or neonatal deaths. We conclude thatoocyte donation to women of advanced reproductive age is highlysuccessful in establishing pregnancy. However, despite carefulantenatal screening, obstetrical complications are common, oftensecondary to multiple gestation.     

Cetrorelix in an oral contraceptive-pretreated stimulation cycle compared with buserelin in IVF/ICSI patients treated with r-hFSH: a randomized, multicentre, phase IIIb study

BACKGROUND: The aim of this study was to assess the non-inferiorityof an oral contraceptive (OC)-pretreated cetrorelix regimenand a buserelin regimen in IVF/ICSI patients treated with r-hFSHin terms of total number of oocytes retrieved. METHODS: Multicentre,randomized study. One hundred and eighty two patients were randomizedto receive cetrorelix with OC pretreatment (n = 91) or to receivebuserelin (n = 91). The cetrorelix group started with dailyOCs on cycle day 5 and continued for 21–28 days. Cetrorelix(0.25 mg) was given daily from stimulation day 6 up to and includingthe day of r-hCG administration. The buserelin group startedwith buserelin (500 µg/day) for at least 10 days untildown-regulation was achieved, after which the dose was reducedto daily 200 µg up to and including the day of r-hCG administration.r-hFSH was started in both groups on a Friday, in the cetrorelixgroup 5 days after the last OC pill intake. Both regimens werefollowed by a standard IVF or ICSI procedure. The primary efficacyendpoint was the number of oocytes retrieved per patient. RESULTS:Number of oocytes, cancellation rates, r-hFSH requirements,number of oocyte retrievals during the weekend or public holidayand number of pregnancies were similar in both groups. Bothtreatment regimens were well tolerated. CONCLUSIONS: Cetrorelixpretreated with OCs resulted in similar number of oocytes retrievedcompared with a long buserelin protocol. Both regimens werewell tolerated and allowed scheduling of the oocyte retrieval,with only small number of retrievals falling on a weekend orpublic holiday.     

Pulsatility index of uterine artery in pregnant and non-pregnant women

In 60 infertile women, 73 uterine arterial pulsatility indices(PI) were measured by transvaginal colour Doppler sonography.The aims were to assess uterine perfusion response in infertilewomen during spontaneous ovarian cycles, and to analyse thechange of uterine perfusion in pregnant cases. The mean PI values(± SD) of 67 non-pregnant cycles were 2.30 (±0.78) in the follicular phase, 2.51 (± 1.05) in the ovulatoryphase and 2.50 (± 0.97) in the mid-luteal phase. Themean PI values (± SD) of six pregnant cycles were 1.67(± 0.22), 1.89 (± 0.41) and 2.23 (± 0.69)in the corresponding phases respectively. The difference betweenthe PI values in the follicular phase for the pregnant and non-pregnantgroups was significant (P < 0.05), as well as that betweenthe follicular and mid-luteal phase for the pregnant group (P< 0.05). There was no significant difference between thePI values in the ovulatory or mid-luteal phase of the two groups.     

Oocyte donation by gamete intra-Fallopian transfer to amenorrhoeic and cycling patients given replacement steroids

Thirteen procedures of oocyte donation by the gamete intra-Fallopiantransfer (GIFT) technique are described. The patients includedsix women with premature ovarian failure, four normally cyclingwomen with unexplained infertility who responded poorly to super-ovulationinduction in preparation for GIFT, and lastly one woman carrierof a 16/21 balanced translocation. Two patients had oocytesdonated on two occasions. Oocyte donors were recruited eitheramong the patients' relatives (n = 4), or among GIFT or IVFpatients (n = 8), who altruistically donated their extra oocytes.Donors were superovulated and oocytes collected laparoscopicallyor vaginally under ultrasound guidance. Donors did not sufferany complications. Recipients were given exogenous oestrogens,and exogenous progesterone was added from the day of donation.Seven clinical pregnancies were obtained (53.8% per attempt);one set of triplets aborted at 14 weeks. Donation took placeon replacement day 12–18 and pregnancies were obtainedin patients receiving oocytes throughout this temporal window.The increasing availability of embryo-freezing facilities willprobably reduce the number of ova available for donation. Therefore,the patients' families may become a precious source of donatedeggs, especially for those patients having large families, withstrong family ties.     

Pregnancy: Premature luteinization as detected by elevated serum progesterone is associated with a higher pregnancy rate in donor oocyte in-vitro fertilization

Premature luteinization has been reported to be associated withdecreased pregnancy rates in patients undergoing in-vitro fertilization.However, the detrimental effect created by a pre-aspirationrise in progesterone is difficult to assess since ovarian stimulationaffects both oocyte quality and endometrial receptivity. Therefore,the relationship between premature luteinization and pregnancyrates remains uncertain. To achieve improved control for confoundingvariables, we studied premature luteinization in ovum donorsof proven fertility. A total of 114 consecutive ovum donationcycles using pituitary suppression with a gonadotrophin-releasinghormone agonist followed by gonadotrophin stimulation were examined.Serum progesterone concentration on the day of administrationof human chorionic gonadotrophin (HCG) was > 1.2 ng/ml in29% of patients. Patients were divided into two groups basedon this value. There was a significant increase in clinicalpregnancy rates per embryo transfer in the group with higherprogesterone concentrations (53 versus 25%, P = 0.012), as wellas significantly more oocytes obtained at aspiration (19.6 ±10.4 versus 13.3 ± 5.4, P < 0.001), and significantlyhigher peak serum oestradiol values (3903 ± 1787 versus2453 ± 1232 pg/ml, P < 0.001). There were no significantdifferences between groups due to age, degree of stimulationor the number of embryos transferred. We conclude that prematureluteinization as based on elevated serum progesterone concentrationis a common occurrence in oocyte donors, reflects healthy folliculardevelopment, and is associated with increased pregnancy rates.     

Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for women undergoing ovarian stimulation for in-vitro fertilization

A total of 100 women undergoing ovarian stimulation with gonadotrophin-releasinghormone agonist (GnRHa) and a human menopausal gonadotrophin(HMG) for in-vitro fertilization (IVF) participated in thisrandomized comparative study. Leuprolide acetate at a dose of0.5 mg/day s.c. (n = 52, group I), or low-dose leuprolide acetatedepot at a dose of 1.88 nig s.c. (n = 48, group II), was startedon days 21–23 of the cycle. Stimulation with 225 IU/dayHMG was started after pituitary desensitization had been achieved.The luteal phase was supported by human chorionic gonadotrophin(HCG) i.m. injection. There were nostatistical differences inbaseline oestradiol (24.5 ± 4.8 versus 21.9 ±4.5 pg/ml) and follicle stimulating hormone (FSH) concentrations(3.9 ± 1.9 versus 3.2 $ 1.8 mlU/ml), and concentrationson the day of HCG administration of oestradiol (1657 ±245 versus 1512$165 pg/ml), luteinizing hormone (LH; 6.2 ±4.8 versus 5.6 ± 4.3 mlU/ml) and FSH (10.6 ± 2.8versus 10.8 ± 3.6 mIU/ml). There were also no statisticaldifferences in the HMG dosage (26.8 ± 1.8 versus 28.5± 1.5), the number of oocytes retrieved (7.6 ±3.0 versus 8.1 ± 4.3), the number of oocytes fertilized(5.3 ± 2.1 versus 5.6 ± 3.0) and the number ofembryos transferred (3.5 ± 1.3 versus 3.4 ± 1.6).There was no evidence of a premature LH surge in either group,but two patients appeared to have a poor response in the leuprolideacetate group (group I). There were 11 pregnancies (21.2%) afterthe use of leuprolide acetate and 12 pregnancies (25.0%) inthose given leuprolide acetate depot; no statistical differenceexisted between these two groups. Thus, an s.c. low-dose leuprolideacetate depot injection may offer a useful alternative for pituitarysuppression in ovarian stimulation for IVF.     

Preimplantation adoption: establishing pregnancy using donated oocytes and spermatozoa

The experience of transferring embryos produced through in-vitrofertilization (IVF) utilizing donated oocytes and spermatozoais described. Recipients (n = 28; aged 38–59 years) receivedoral micronized oestradiol and i.m. progesterone and were synchronizedto donors undergoing ovarian stimulation. Reasons for selectingtherapy included advanced reproductive age (>42 years; n= 21) or hyper-gonadotrophic hypogonadism (n = 7), combinedwith severe male factor infertility in 23 couples. Five womenwere single and without partners. Oocytes were fertilized bycryopreserved spermatozoa designated for use by the recipient.Up to five embryos were transferred trans-cervically. Supernumeraryembryos were cryopreserved. A total of 36 aspirations produced15.6 ± 7.3 oocytes per retrieval. In 10/36 cycles (27.8%),embryos were available for cryopreservation. Using fresh embryos,the overall pregnancy rate was 38.9% (14/36), clinical pregnancyrate 33.3% (12/36), and ongoing/delivered pregnancy rate 30.6%(11/36). Three ongoing pregnancies were later established bytransferring cryopreserved embryos. Adjusting for these events,the per aspiration overall pregnancy rate per retrieval was47.2%, clinical pregnancy rate 41.7%, and ongoing/deliveredpregnancy rate 38.9%. Implantation rates per individual embryotransferred were 16.6% following fresh embryo transfer. A viablepregnancy was achieved by 14 of 28 women (50% cumulative pregnancyrate). We conclude that using donor oocytes and donor spermatozoais efficacious and allows couples of whom both members sufferfrom severe gamete abnormalities and single functionally agonadalwomen an effective means of achieving pregnancy.     

The effect of smoking and varicocele on human sperm acrosin activity and acrosome reaction

Smoking and varicocele are frequent findings in the medicalhistory and physical examination of patients attending and rologicaloutpatient departments. However, data about their influenceon human semen parameters, such as sperm concentration and motility,are contradictory. Therefore, the purpose of this study wasto examine sperm function (acrosin activity and induction ofthe acrosome reaction) in smokers (n = 130) and varicocele patients(n = 30)compared with normal fertile donors (n = 20). The acrosomereaction was detected by triple staining after 3 h ofincubationat 37°C, followed by treatment with 0.1%dimethyl sulphoxide(spontaneous acrosome reaction) and 10 µM calcium ionophoreA23187 (induced acrosome reaction) for 1 h at 37°C. Acrosinactivity was measured by gelatinolysis. The diameters aroundthe sperm heads after gelatinolysis and the percentages of spermatozoashowinghalo formations were evaluated. The inducibility of theacrosome reaction was significantly lower in semen samples fromsmokers than in those from the fertile group (7.1 ±3.2versus 11.2 ± 4.0%, P < 0.01), whereas no statisticallysignificant difference was demonstrated in spermatozoa frompatients with varicocele (9.3 ± 4.3%). Both the percentagesof spermatozoa with halo formation (53.3 ±20.0 versus76.6 ± 13.6%, P < 0.05) and the halo diameters (16.1± 6.6 versus 31.0 ± 14.5 urn, P < 0.001) weresignificantly lower in the varicocele group than in thesamplesfrom fertile men. These data suggest that smoking and varicoceleaffect sperm function, and that the standard semen parametersalone are insufficient to evaluate the influence of both factorson human male fertility.     

Human and bovine cervical mucus penetration as a test of sperm function for in-vitro fertilization

Human and bovine cervical mucus penetration tests (n = 57) wereperformed preceding IVF to test their prognostic value as spermfunction tests for IVF. This evaluation also induded resultsfrom conventional semen analysis and from a computerized spermanalysis system. The bovine cervical mucus penetration testwas shown to be at least as valuable as the human cervical mucuspenetration test in evaluating sperm function. The migrationdistance of the vanguard sperm (P < 0.001) and the spermdensity at a fixed migration distance in the mucus column (P< 0.05) correlated most closely with the IVF results. A clearparallelism with the out come of the ‘swim up’ techniquewas also found. Of the sperm parameters examined, only spermmotility In the ejaculate (P < 0.05) correlated significantlywith the results of IVF. It is concluded that the outcome ofa bovine cervical mucus penetration test depends on the samesperm functions as re quired for IVF. Therefore, this test maybe of predictive value in an IVF programme.     

Andrology: The presence of Mullerian inhibiting substance in human seminal plasma

Müllerian inhibiting substance (MIS), produced by testicu-IarSertoli cells, is present in adult male serum. The first aimof this study was to determine if MIS is present in seminalplasma. Using an enzyme-linked immunosorbent assay (ELISA),we measured MIS concentrations in seminal plasma from 23 donorsexhibiting normal (WHO criteria) sperm qualities, and 169 patientswith subnormal sperm parameters. The second aim of this studywas to examine a potential relationship between MIS and spermmotility. MIS concentrations in seminal plasma ranged from 0.5to 3.6 ng/ml in donors and from 0.5 to 17.8 ng/ml in patients.Motility index (MI, mean ± SEM) for all patient sampleswas lower compared with donors (113.3 ± 3.2 and 1983± 13.5, P < 0.00001), while mean MIS concentration(± SEM) was higher (4.2 ± 03 and 1.4 ±0.2, P < 0.0003). When the patients were stratified intoGroups I (motility < 50%, n = 42) and D (motility >50%,n = 127), the MI (mean ± SEM) values were 623 ±3.8 and 130.2 ± 2.7 respectively (P < 0.0001 for bothcompared with donors) and mean MIS concentrations (±SEM) were 5.4 ± 0.6 and 3.9 ± 03, respectively(P < 0.0001 and P < 0.001 compared with donors). The inverserelationship between MIS concentration in seminal plasma andmotility index suggests that MIS may have a function in modulatingmotility.     

Endocrinology: Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial

Two different regimens of luteal support in gonadotrophin hormone-releasinghormone (GnRH) analoguefhuman menopausal gonadotrophin (GnRHa/HMG)-inducedin-vitro fertilization cycles (IVF) were compared in a randomizedclinical trial. After embryo transfer, either vaginal progesteronealone was administered (n=89, P group), or a combination ofvaginal progesterone and human chorionic gonadotrophin (n=87,P/HCG group). The primary aim of this study was to assess theeffect of the different regimens of luteal support on the pregnancyrate. The secondary aim was to compare oestradiol and progesteroneconcentrations in the luteal phase between the two groups, andassess their effect on the pregnancy rate. A clinical pregnancyrate of 15% was found in the P/HCG group in comparison with26% in the P group (odds ratio 0.49; 99% confidence interval:0.18–1.3). The luteal serum oestradiol and progesteronevalues in the P/HCG group were significantly higher when comparedwith the P group on the 6th, 9th and 12th day after oocyte retrieval(Wilcoxon P<0.001). In accordance with the high oestradiolconcentrations, more cases of ovarian hyperstimulation syndrome(OHSS) were found in the P/HCG group. Oestradiol values on the9th day after oocyte retrieval, presumably the day of implantation,appeared to be higher in women who did not become clinicallypregnant. We conclude that vaginal progesterone alone providessufficient luteal support in GnRHa/HMG induced IVF cycles. Thecombination of vaginal progesterone and HCG as luteal supportleads to significant high luteal oestradiol and progesteroneconcentrations. But a high concentration of oestradiol seemsto have a deleterious effect on the implantation process, resultingin a low pregnancy rate.