Infertility: A randomized, assessor-blind, group-comparative efficacy study to compare the effects of Normegon(R) and Metrodin(R) in infertile female patients undergoing in-vitro fertilization

A randomized, assessor-blind, group-comparative study was performedto compare the efficacy of Normegon^® [75 IU follicle stimulatinghormone (FSH) and 25 IU luteinizing hormone (LH)] and Metrodin^®(75 IU FSH and <1.25 IU LH) in infertile women undergoingin-vitro fertilization (IVF) and embryo transfer. None of thepatients were pituitary-suppressed by means of gonadotrophin-releasinghormone (GnRH)-agonist treatment. They were randomized in blocksof five with a ratio between treatment with Normegon and withMetrodin of 3: 2. A total of 158 patients started hormonal treatment,i.e. 93 patients with Normegon and 65 patients with Metrodinand a total of 248 cycles were performed. Evaluation of firsttreatment cycles included statistical analysis of the totalnumber of ampoules, number of follicles (14 mm), serum oestradiolconcentrations on the day of HCG (10 000 IU) administration,the number of oocytes retrieved and the ongoing pregnancy rateper attempt and per transfer. For none of these parameters weresignificant differences revealed. In both groups the medianduration of stimulation was 7 days and the median number ofampoules used was 21. Overall, the duration of treatment wasshort in order to prevent as much as possible endogenous LHrises. The overall ongoing pregnancy rate per transfer of allcycles was 21% in the Normegon group and 19% in the Metrodingroup. Analysis of completed treatment cycles (n = 90) withpremature rises of LH >10.0 IU/l and/or progesterone >1.0ng/l revealed a relatively high incidence (23%) of fertilizationfailure and poor embryo quality, but the ongoing pregnancy rateper transfer was still 22%. These data suggest that prematurerises of LH and progesterone are deleterious for oocyte qualitybut may not affect the endocrine environment of the endometrium.In conclusion, Normegon is an efficacious preparation for theinduction of ovarian stimulation in infertile women undergoingIVF.     

Anthropometric indicators and response to gonadotrophin for ovulation induction

A total of 111 women with no ultrasonographic findings of polycysticovarian syndrome were observed between January 1989 and December1991 in an in-vitro fertilization (IVF) programme. The treatmentschedule involved ovulation induction after treatment with agonadotrophin-releasing hormone (GnRH) agonist, using standarddoses of human menopausal gonadotrophin (HMG) for 4 days, andfurther stepwise increments in dosage as required. Responseto the treatment was defined as: (i) presence/absence of oneor more follicles 10 mm diameter after 4 days of treatment,and (ii) oocyte retrieval. Three indices of body mass were considered:weight (W) in kg/height (H)² in metres (Quetelet‘s index),W/H1–^1.5 (the National Health and Nutrition ExaminationSurvey anthropometric index for women), W0–^0.30/H (ponderalindex). Surface area was computed as 0.0235 (H in cm^0.422) (Win kg^0.515). Women in the upper tertiles of the range of anthropometricindicators more frequently tended to present no follicle 10mm on day 7. Likewise, oocytes were retrieved less frequentlyin subjects in the higher tertile than in those in the lower.The odds ratio of a negative response both on day 7 and at theend of treatment increased with the tertiles of body mass indicesor surface areas. This study suggests that response to ovulationinduction treatment is inversely related to body mass index     

Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study

The effect of doubling the human menopausal gonadotrophin (HMG)dose in the same treatment cycle in which the ovarian responseafter 5 days of ovarian stimulation with 225 IU/day is ‘low’,has been evaluated in a prospective randomized study. Forty-sixpatients met the ultrasound and oestradiol criteria for enrolmentin the study, one patient participated twice. In 22 patientstreatment was continued with 225 IU HMG/day and in 25 patientsthe HMG dose was increased to 450 IU/day. No effect of doublingthe HMG dose was found on the length of the ovarian stimulation,peak oestradiol values, number of follicles 11 and 14 mm indiameter respectively on ultrasound on the day of HCG administration,number of cancelled cycles, number of oocytes at follicularpuncture and the number of patients with 3 oocytes at retrieval.It is concluded that doubling the HMG dose in the course ofan IVF treatment cycle is not effective in enhancing ovarianresponse in low responders. This is in accordance with currenttheories on follicular growth, which state that follicular recruitmentoccurs only in the late luteal and early follicular phase ofthe menstrual cycle.     

Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation

This multicentre, randomized study was performed to assess theefficacy and safety of 0.25 mg ganirelix (Orgalutran^®, Antagon^TM)treatment, using triptorelin (Decapeptyl^®) in a long protocolas a reference treatment. In total, 236 subjects were randomizedto treatment with ganirelix (0.25 mg, s.c.) and 119 to triptorelin(0.1 mg, s.c.) treatment (treatment ratio 2:1). Treatment withganirelix started on day 6 of stimulation, whereas treatmentwith triptorelin started on menstrual cycle day 21 to 24 ofthe previous cycle (i.e. the midluteal phase). The ganirelixregimen was on average 17 days shorter (9 versus 26 days) comparedto the triptorelin regimen. The median total dose of recombinantFSH (Puregon^®) used was 450 IU less (1350 versus 1800 IU)in the ganirelix protocol. The initial follicular growth wasfaster and, consequently, oestradiol concentrations were higherin the ganirelix group. On the day of human chorionic gonadotrophin(HCG), the mean number of follicles 11 mm was 10.1 and 10.7and the median serum oestradiol concentration was 1090 and 1370pg/ml in the ganirelix and triptorelin groups respectively.Per attempt, 7.9 and 9.6 oocytes (mean) were retrieved in theganirelix and triptorelin groups respectively. The fertilizationrates (64.0% ganirelix and 64.9% triptorelin) and the mean numberof good quality embryos (2.7 and 2.9) were comparable in bothtreatment groups. The implantation rate was identical (22.9%).The ongoing pregnancy rate per attempt was 31.0 and 33.9% inthe ganirelix and triptorelin groups respectively. The ganirelixregimen showed an improved local tolerance in that the percentageof subjects with at least one local skin reaction was 2-foldlower than in the triptorelin group (11.9 versus 24.1%). Takingall data together, it may be concluded that ganirelix offersa new treatment regimen in ovarian stimulation that is short,safe and well-tolerated, optimizing convenience for the patient.     

Infertility: The prognosis for assisted conception treatment after unexpected failure of fertilization in vitro: a comparative study

The relative prognosis for further assisted conception treatment(without micro-injection) after initial unexpected failure offertilization in apparently favourable couples undergoing in-vitrofertilization (IVF) treatment was assessed. After their firstcycle of treatment, 481 consecutive couples were grouped accordingto their fertilization (including cleavage) rate per oocyteinto five bands. Proportions of couples proceeding to furthercycles of treatment by IVF or gamete intra-Fallopian transfer(GIFT) and resulting fertilization and pregnancy rates werecompared. Pregnancy rates in the first cycle of treatment weresignificantly related to fertilization rate. The fertilizationrate was zero in 13 couples (3%) and only 1–24% in 18(4%). There were no significant differences between these groupsin the proportions proceeding to further treatment (31, 50%)compared with others (overall 37%, including some treated byGIFT), or in their median fertilization rates (75, 60% comparedwith 67% – IVF cycles only), pregnancy rates (20, 38%of cycles compared with 37% – IVF or GIFT) or birth rates(20, 38% of cycles compared with 31% – IVF or GIFT). Amongstcouples whose initial fertilization rate was 50% there wasno fertilization in 4% of subsequent IVF cycles. We concludethat in couples with well defined favourable conditions, includingtests of sperm function for assisted conception treatment, whohave unexpected failure of fertilization, the prognosis forfurther treatment remains favourable without resort to morecomplex investigations or micro-injection methods. Such failureoccurs infrequently and generally as a random event, and shouldhave no appreciable effect on life-table calculation of cumulativepregnancy and birth rates in this group of patients.     

Pregnancy: Adverse effect of a homogeneous hyperechogenic endometrial sonographic pattern, despite adequate endometrial thickness on pregnancy rates following in-vitro fertilization

We have previously presented data to show that in patients whohad in-vitro fertilization (IVF)—embryo transfer usingovarian stimulation involving the luteal phase leuprolide acetate—humanmenopausal gonadotrophin (HMG) regimen, poor pregnancy resultsensued if either the endometrial thickness was < 10 mm ora homogeneous hyperechogenic sonograpic pattern was presentimmediately prior to taking a human chorionic gonadotrophin(HCG) injection. There were only 15 cases with this hyperechogenictype endometrium (and no pregnancies). The purpose of the presentstudy was to evaluate the influence of a hyperechogenic endometriumwhen the endometrial thickess was 10 mm, in a more extensiveseries, in women having IVF—embryo transfer using thesame ovarian stimulation regimen. A total of 273 consecutivecycles, where endometrial thickness was 10 mm, were evaluated(not including the 85 cycles previously reported). Of 22 patientswith the hyperechogenic pattern, one achieved a chemical pregnancy(-HCG >500 mIU/ml) and none achieved clinical pregnancies(ultrasound confirmation). In contrast, 67 of 251 (26.7%) patientsconceived with other echo patterns (x² analysis = 5.9, df =1, P = 0.01). These data thus confirm, in a larger series, thenegative influence of this type of echo pattern on subsequentpregnancy rates following the luteal phase leuprolide acetate—HMGovarian stimulation regimen.     

Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol

BACKGROUND: Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol. METHODS: 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG. RESULTS: Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively). CONCLUSIONS: Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.     

Comparison of two recombinant follicle-stimulating hormone preparations in in-vitro fertilization: a randomized clinical study.

A randomized comparison of two recombinant human follicle-stimulating hormone (recFSH) preparations (Gonal-F and Puregon) in ovarian stimulation for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was carried out at the Infertility Clinic of the Family Federation of Finland. A total of 348 women (aged 22-43 years) suffering from infertility due to miscellaneous causes was recruited. Of these, 344 underwent stimulation using equal starting doses (150 IU/day: Gonal-F n = 164, Puregon n = 158 or 300 IU/day: Gonal-F n = 8, Puregon n = 14) after down-regulation with intranasal buserelin from the mid-luteal phase. Similar clinical pregnancy rates were achieved with both preparations; 33.5% per cycle and 37.4% per embryo transfer (24.5% one-embryo and 75.5% two-embryo transfers, n = 147) with Gonal-F (150 IU/day) and 32.9% per cycle and 36.4% per embryo transfer (30.1% one-embryo and 69.9% two-embryo transfers, n = 145) with Puregon (150 IU/day). The ongoing cumulative pregnancy rates after frozen-thawed embryo transfer were 35.4% with Gonal-F and 37.7% with Puregon. Six cycles were cancelled because of a low response (three in each group). Similar numbers of oocytes were obtained in both groups; 13.0 with 150 IU/day and 6.1 with 300 IU/day Gonal-F, and 12.4 with 150 IU/day and 7.1 with 300 IU/day Puregon. The fertilization and cleavage rates and the incidence of moderate or severe ovarian hyperstimulation syndrome (Gonal-F, 2.0% and Puregon, 0.7%) were also similar. Gonal-F and Puregon were equally and highly effective in stimulation for IVF and ICSI.     

Pregnancy: Coffee and alcohol intake, smoking and risk of multiple pregnancy

We analysed the relationship between coffee and alcohol intake,smoking and risk of multiple pregnancies using data from a case-controlstudy on risk factors for multiple births conducted in Italy.Cases were 133 women who delivered multiple births not relatedto treatment for infertility (33 monozygotic and 100 dizygotictwins). Controls were 395 women admitted for normal deliveryat the same clinic where cases had been identified. The oddsratios (OR) of multiple pregnancy were 1.5 [95% confidence interval(CI) 0.8–2.8] and 2.0 (95% CI 1.0–3.7) for womendrinking respectively one to two or three or more cups of coffeeper day in comparison with non-coffee drinkers. Consideringseparately dizygotic and monozygotic pregnancies, the estimatedOR were respectively for women drinking three or more cups ofcoffee, 1.7 and 3.1 for dizygotic and monozygotic pregnancies.The risk of multiple pregnancy tended to be higher in womendrinking 15 alcohol drinks per week: in comparison with tea-totallersthe estimated OR for drink 15 glasses per week were 23 and 2.6respectively for dizygotic and monozygotic pregnancies. Heavysmokers (10 cigarettes per day) were at increased risk of multiplepregnancy: in comparison with never smokers, the estimated ORfor multiple pregnancy was 1.6 (95% CI 0.9–2.7). Consideringseparately the two groups of multiple pregnancy, the OR of dizygoticand monozygotic pregnancy were 1.4 (95% CI 0.8–2.5) and2.4 (95% CI 0.9–6.1) for women smoking 10 cigarettes/day, but the trend in risk with number of cigarettes smokedper day and duration of the habit was not significant.     

Efficacy and safety of recombinant follicle stimulating hormone (Puregon(R)) in infertile women pituitary-suppressed with triptorelin undergoing in-vitro fertilization: a prospective, randomized, assessor-blind, multicentre trial

The objective of this study was to compare the efficacy andsafety of a recombinant follicle stimulating hormone (FSH) preparation(Org 32489, Puregon^®) with a urinary FSH preparation (Metrodin^®)in infertile women undergoing in-vitro fertilization (IVF andembryo transfer and who were pituitary-suppressed with triptorelin.In an assessor-blind, group-comparative, multicentre study,60 women were randomized to Org 32489 and 39 to urinary FSH.An evaluation of the main parameter, the mean total number ofoocytes recovered, indicated a similar efficacy for the twopreparations: 9.7 with Org 32489 versus 8.9 with urinary FSH.In addition, there were no significant between-group differenceswith respect to other efficacy variables such as the total doseused, the duration of the treatment, the number of follicles17 mm in diameter and embryo quality. The ongoing pregnancyrates per attempt (30.2 versus 17.4%) and per transfer (34.0versus 18.8%) were higher with Org 32489, but this differencewas not statistically significant. No clinically relevant differencesbetween Org 32489 and urinary FSH were seen with respect tosafety variables. Serum antibodies were not detected in anyof the subjects. It is concluded that Org 32489 compares favourablywith urinary FSH in the treatment of infertile pituitary-suppressedwomen undergoing IVF and embryo transfer.     

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.     

Endocrinology: The empty follicle syndrome: a pharmaceutical industry syndrome

The purpose of this study is to provide evidence that emptyfollicle syndrome (EFS) is a result of an abnormality in thein-vivo biological activity of some batches of commerciallyavailable human chorionic gonadotrophin (HCG). This is a comparativestudy between six consecutive in-vitro fertilization (IVF) caseswith EFS (study group) and 10 IVF pregnancy cycles (controlgroup). Both groups received the same ovarian stimulation protocolconsisting of leuprolide acetate and human menopausal gonadotrophin(HMG). An i.m. injection of 10 000 IU of HCG was administeredonce follicles had reached 18–20 mm and oestradiol/follicle16 mm was at least 900 pmol/l. Transvaginal aspiration was performed36 h later. Plasma HCG prior to and 12 h after i.m. injectionas well as the follicular fluid (FF) concentrations of oestradiol,progesterone, luteinizing hormone (LH) and HCG were determinedin the study group and controls. The in-vitro biological activityof the batch of HCG used by the EFS cases and the control groupwas determined using a Leydig cell preparation from adult rats.Furthermore, the plasma clearance rate after i.v. injectionof 5000 IU of HCG, from the same batches, was studied in threemale volunteers. In the IVF cycles, no HCG was detected in plasmaprior to the injection of commercial HCG. After 12 h, no HCGwas detected in the study group compared to a mean of 207.5IU/l (110–360) in controls. Mean FF concentration of LH,HCG, progesterone and oestradiol was 0.9 IU/1, 0 IU/l, 3.1 nmol/mland 4.4 nmol/ml in EFS compared to 1.0, 98.3, 32.0 and 3.7 inpregnancy cycles. The in-vitro biological activity in both HCGbatches was not significantly different; however, immunoreactiveHCG used in EFS cases was undetectable in plasma of male volunteersas soon as 10 min after i.v injection of 5000 IU of HCG. Theendocrine abnormalities found in follicular fluids of EFS arenot a consequence of an ovarian problem but the result of alack of exposure to biologically active HCG. The rapid clearanceof the drug after i.v. injection and the high affinity of desialylatedHCG to liver cells suggest this to be a possible explanationfor this infrequent but unfortunate event.     

Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success

BACKGROUND: Although laparoscopic ovarian drilling (LOD) hasbeen widely used to induce ovulation in women with polycysticovarian syndrome (PCOS), predicting the clinical response tothis treatment remains to be elucidated further. This studywas carried out to identify factors that may help to predictthe outcome of LOD. METHODS: This retrospective study included200 patients with anovulatory infertility due to PCOS who underwentLOD between 1990 and 2002. The influence of the various patients'pre-operative characteristics on the ovulation and pregnancyrates after LOD was evaluated. In addition, women were dividedinto two or three categories according to the severity of eachof the various clinical and biochemical parameters of PCOS.The success rates were compared between the categories of eachfactor using contingency table analyses. Multiple logistic regressionanalysis was used to identify independent predictors of successof LOD. RESULTS: Women with body mass index (BMI) 35 kg/m²,serum testosterone concentration 4.5 nmol/l, free androgen index(FAI) 15 and/or with duration of infertility >3 years seem tobe poor responders to LOD. In LOD responders, serum LH levels>10 IU/l appeared to be associated with higher pregnancy rates.CONCLUSION: Marked obesity, marked hyperandrogenism and/or longduration of infertility in women with PCOS seem to predict resistanceto LOD. High LH levels in LOD responders appear to predict higherprobability of pregnancy.     

Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection

An ultrasonographic evaluation of the endometrium was performedin 158 patients undergoing ovarian stimulation for an in-vitroassisted reproduction programme. Endometrial thickness was evaluatedin 109 patients undergoing in-vitro fertilization (IVF) forfemale indications and in 49 patients undergoing intracytoplasmicsperm injection (ICSI) for male indications. The maximal endometrialthickness was measured on the day of human chorionic gonadotrophin(HCG) administration by longitudinal scanning of the uteruson the frozen image using electronic callipers placed at thejunction of the endometrium-myometrium interface at the levelof the fundus. Cases in which the endometrial thickness was10 mm were included in group A; cases in which the endometrialthickness was <10 mm were assigned to group B. The age ofthe patients, serum 17- oestradiol concentrations on the dayof HCG administration, the length of follicular stimulation,the number of follicles, 17- oestradiol concentrations per follicleon the day of HCG and the number of embryos transferred wereanalysed in each case. When comparing endometrial thicknessand results in IVF and ICSI patients, an endometrium <10mm predominated in IVF patients (27.5%) compared with thoseundergoing ICSI (16.7%) (P=0.05); conversely an endometrium10 mm was more frequent in ICSI than in IVF patients. The incidenceof pregnancy was higher in IVF group A patients (32/79; 41%)than in IVF group B patients (5/30; 17%) (P=0.03), whereas nosignificant difference was found between ICSI group A (13/42;31%) and ICSI group B (3/7; 43%) patients. Thus, a higher percentageof IVF patients had thin endometrium when compared with ICSIpatients; thin endometrium was a prognostic indicator of pregnancyonly in the case of a female indication for infertility (IVF).A thin endometrium in cases of female infertility may reflecta previous or present uterine pathology, whereas in indicationsof male infertility (i.e. cases using ICSI), in the absenceof any associated uterine pathology, the presence of a thinendometrium is not predictive.     

Endocrinology: Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization

The present study was undertaken to assess whether the increasein serum progesterone concentration following the administrationof human chorionic gonadotrophin (HCG) may have predictive valueon the in-vitro fertilization (IVF) success rate. Progesteroneconcentration on the day of HCG administration and the increasein progesterone concentration on the following day were evaluatedin 140 consecutive patients undergoing IVF with embryo transfer.Stimulation protocol in all study patients entailed intranasaladministration of short-acting gonadotrophin-releasing hormoneagonist (GnRHa) buserelin and human menopausal gonadotrophin.A pregnancy rate of 37.2% was achieved when at least three embryoswere transferred. The only significant difference between conceptionand non-conception cycles was found in serum progesterone concentrationsafter HCG administration (P < 0.01), whereas the mean progesteroneconcentration on the day of HCG did not differ. No differencein other hormonal or cycle parameters was observed. The increasein progesterone concentration was significantly greater in thegroup of patients who achieved pregnancy than in the group whodid not (2.2 ± 0.2 versus 1.6 ± 0.1 ng/ml, respectively;P < 0.01). A critical breakpoint in serum progesterone wasarbitrarily determined at 1 ng/ml. An increase in progesteroneconcentration 1 ng/ml when three or more embryos were transferredwas associated with a positive predictive value for pregnancyof 40.4% (sensitivity of 94.7%), whereas a negative predictivevalue of 86.7% was obtained when this value was <1 ng/ml.These findings indicate that an adequate rise in serum progesteronefollowing HCG administration provides useful information aboutthe possible outcome of the treated cycle.     

Accumulation of human chorionic gonadotrophin in the serum of patients during in-vitro fertilization treatment cycles with Pergonal

We examined the possible contribution of human chorionic gonadotrophin(HCG) in Pergonal to the serum luteinizing hormone (LH)-likebioactivity in 10 patients (median age32 years, range 28–38)with tubal infertility who were undergoing in-vitro fertilization(IVF), together with 19 controls (median age30 years, range21–43). IVF patients were treated with clomiphene (50mg twice daily) over days 2–6 and Pergonal (150 IU i.m.)daily from day 5 until at least day 10. Serum LH was measuredby fluoro-immunometric assay (I-LH) and in-vitro Leydig cellbioassay (B-LH). Serum HCG was measured by fluoro-immunometricassay. The data were analysed by paired two-tailed t-test, followinglogarithmic transformation. From days 1–5, there was anincrease in serum B-LH (mean, 95% confidence intervals givenin parentheses) from 8.3 (6.8, 10.2) IU/1 to 11.7 (9.8, 13.9)IU/1 [P= 0.004], and in serum I-LH from 4.5 (3.7, 5.4) IU/1to 5.4 (4.6, 6.3) IU/1 [P= 0.002]. From days 5–8, therewas a rise in B-LH to 16.6 (12.6, 21.9) IU/1 [P= 0.023]. Therise in I-LH to 6.3 (5.1, 7.8) IU/1 [P= 0.081] failed to reachsignificance. Furthermore, serum HCG was <<0.75 IU/1 untilafter Pergonal was administered on day 5, then rose to a plateauon day 8 at 1.2(0.8, 1.6) IU/1. Serum HCG in the controls remained<<0.75 IU/1 throughout. We conclude there is a disproportionateincrease in serum B-LH compared to I-LH from days 5–8,corresponding with a rise in serum HCG and the commencementof treatment with Pergonal. The HCG in Pergonal may be contributingto an undesirable rise in serum LH-like bioactivity, which mightreduce the success rate of IVF.     

Pregnancy: Alcohol and risk of spontaneous abortion

The objective of this study was to assess the association betweenalcohol drinking before and during pregnancy and the risk ofspontaneous abortion using data from a case-control study conductedin Milan, Italy. A total of 462 women (median age 30 years)were admitted for spontaneous abortion (within the 12th weekof gestation) to a network of obstetrics departments in thegreater Milan area. Of these, 148 (32%) were between the fourthand the eighth week of gestation and 314 (68%) between the ninthand the 12th week. A control group was made up of 814 women(median age 29 years) who gave birth at term (>37 weeks gestation)to healthy infants (Apgar 5th minute 8, weight 3000 g) on randomlyselected days at the same hospitals where cases had been identified.A total of 212 cases (46%) and 355 controls (47%) reported alcoholdrinking before conception. Considering non-drinkers as thereference category, the relative risks (RR) of spontaneous abortionwere 1.2 (95% confidence interval (CI), 0.9–1.6] and 0.8(95% CI, 0.6–1.1), respectively, in drinkers of one toseven and more than seven drinks per week before conception.No association emerged between the duration of alcohol drinkingand the risk of spontaneous abortion. A total of 166 cases (35.9%)and 263 (32.3%) controls reported any alcohol drinking duringthe first trimester of pregnancy. The corresponding relativerisk was 1.1 (95% CI, 0.9–1.4) and no relationship emergedbetween the number of drinks per week and the risk of abortion.Likewise, maternal wine and beer drinking in the first trimesterof pregnancy was not associated with the risk of spontaneousabortion. Evidence available from this and previous studies,although partially controversial, indicates that moderate (oneor two drinks per day) alcohol consumption does not increasemarkedly the risk of miscarriage.     

Immunology: Intravenous immunoglobulin for in-vitro fertilization failure

The aim of this study was to determine the effectiveness ofintravenous (i.v.) immunoglobulin (Ig) for treatment of individualsexperiencing failure after in-vitro fertilization (IVF) andembryo transfer. A total of 29 women with unexplained infertilitywho failed to become pregnant after IVF/embryo transfer weredivided into two groups based on performance in previous IVFcycles: 16 women had fertilization of 50%of oocytes retrievedand/or produced 3 embryos each cycle and 13 had fertilizationof<50% of oocytes retrieved and/or produced <3 embryoseach cycle. Each woman had received at least 12 transferredembryos (95th percentile for successful IVF patients) or hadexperienced two or more biochemical pregnancies without ultrasonicconfirmation of implantation during previous IVF/embryo transferattempts. All women received i.v. Ig 500 mg/kg prior to thenext embryo transfer. Only one of the 13 (8%) women with suboptimalfertilization and embryo yield became pregnant in the treatmentcycle. Of 16 women who had previously had fertilization of atleast 50% of oocytes retrieved and produced at least three embryos,nine (56%) became pregnant in the treatment cycle. The differencein pregnancy rates between the two groups is significant (P=0.02).Intravenous Ig is useful in the treatment of unexplained IVFfailure in women who have oocyte fertilization rates 50% andgenerate at least three embryos per cycle.     

A comparative analysis of embryo implantation potential in patients with severe teratozoospermia undergoing in-vitro fertilization with a high insemination concentration or intracytoplasmic sperm injection

The objective of this study was to assess fertilization, implantationand pregnancy rates in infertile patients with severe teratozoospermia[P (poor prognosis) pattern sperm morphology assessed by strictcriteria] treated by in-vitro fertilization (IVF) using a highinsemination concentration (HIC), or by intracytoplasmic sperminjection (ICSI). This was a retrospective cohort study performedin an academic tertiary institution. The outcome of 115 consecutiveICSI cycles was compared to that of a similar number of cyclesof IVF with HIC performed during a similar time frame and matchedby woman's age and basal serum (cycle day 3) follicle stimulatinghormone concentrations. The inclusion criteria were sperm morphology4% normal forms (P pattern) and 1 x106 total motile spermatozoaper ejaculate. The diploid fertilization rate in the HIC-IVFgroup was 86% and in the ICSI group 68% (P < 0.05). Importantly,an equal number of embryos was transferred to both groups ofpatients. The morphological quality of the embryos (proportionof transfers having superior morphology embryo scores) was significantlybetter in the ICSI group than in the patients receiving HIC-IVF.Although there was a clear trend for better implantation andpregnancy rates in the ICSI group, these differences were notstatistically significant We conclude that, although HIC-IVFresulted in a higher fertilization rate than ICSI in patientswith severe teratozoospermia, ICSI produced a significantlyhigher proportion of morphologically superior embryos with atendency towards a higher implantation potential. Therefore,teratozoospermic patients having adequate numbers of motilespermatozoa should be offered ICSI as an alternative to modified(HIC) IVF treatment.     

An aggressive philosophy in controlled ovarian stimulation cycles increases pregnancy rates

To assess the effect of timing of human chorionic gonadotrophin(HCG) administration in ovarian stimulation cycles, the serumoestradiol concentration and follicle profile were comparedwith the clinical pregnancy rate in 582 ovarian stimulation— intra-uterine insemination (OS—IUI) cycles and3917 in-vitro fertilization—embryo transfer (IVF—ET)cycles. The pregnancy rates increased exponentially with increasingoestradiol in both OS—IUI and IVF—ET cycles (R²= 0.720, P < 0.001) but then decreased in OS-IUI cycles whenthe oestradiol concentration exceeded 5000 pmol/l (R² = 0.936,P < 0.004) at HCG administration. In OS—IUI cyclesthe percentage of cycles with three or more mature follicles( 18 mm diameter) increased up to an oestradiol concentrationof 5000 pmol/l then declined, mirroring the pregnancy rate (R²= 0.900, P = 0.01). The exponential increase in pregnancy ratewith increasing oestradiol concentration in IVF—ET cyclessuggests that high oestradiol concentration does not have adeleterious effect on endometrial receptivity. The decreasein pregnancy rate in OS-IUI cycles when oestradiol concentrationexceeded 5000 pmol/l reflected fewer mature follicles, resultingfrom premature administration of HCG to avoid severe ovarianhyperstimulation syndrome (OHSS). We recommend that HCG administrationbe delayed until multiple follicles have reached maturity, andreducing the risk of severe OHSS by converting high risk OS—IUIcycles to IVF—ET, or if funds or facilities are unavailable,transvaginally draining all but four or five mature follicles.