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.     

Andrology: Strategies in frozen donor semen procreation

Data were analysed from 710 couples who had been assessed todetermine the effectiveness and the drawbacks of three differentmethods of insemination using frozen donor semen. Intracervicalinsemination (ICI) was the first method used when the womenhad no tubal disorder: 255 pregnancies were achieved in a totalof 2558 cycles (10%). Intrauterine insemination (IUI) associatedwith ovarian stimulation resulted in 152 pregnancies over 966cycles (16%). In-vitro fertilization (IVF) was proposed after12 insemination failures using either of the other methods orwhen the initial gynaecological examination had revealed abnormalitiessuch as tubal occlusions; 48 pregnancies were obtained in 262cycles (18.3%). The pregnancy rate using ICI was significantlyhigher when two inseminations were performed per cycle, comparedwith one insemination per cycle (12.3 versus 7%, P < 0.001).The number of motile spermatozoa per straw was correlated withthe pregnancy rate when using ICI, rising from 9% with <4X10⁶motile spermatozoa to 13.8% with 4–8X10⁶ and 17.2% with>8X10⁶. No relationship was found between the number of motilespermatozoa and the pregnancy rate using IUI and IVF. The incidenceof primary ovulatory disorder was higher among women whose husbandswere oligozoospermic than among those whose husbands were azoospermic(19 versus 9%, P < 0.01), but ovarian stimulation improvedthe fecundity of subfertile women. The outcome of pregnancieswas also analysed for the three methods. From these data, strategicplans have been proposed to maximize the pregnancy rate forwomen undergoing therapeutic donor insemination with frozensemen.     

Fallopian tube sperm perfusion (FSP) versus intra-uterine insemination (IUI) in the treatment of unexplained infertility: a prospective randomized study

Prospective randomization of 60 couples with unexplained infertilitywas performed for treatment either with intrauterine insemination(IUI), using a volume of 0.5 ml of the inseminate, or Fallopiantube sperm perfusion (FSP), using a volume of 4 ml of inseminate.The protocols for ovarian stimulation and induction of ovulationwere the same in the two groups. The two groups were similarconcerning age of the female at the start of treatment and thenumber of follicles > 15 mm diameter, the serum oestradiolconcentrations and the endometrial thickness on the day of humanchorionic gonadotrophin (HCG) administration. The mean (±SD)number of motile spermatozoa inseminated was significantly higherin the FSP group than in the IUI group (52 ± 5 x 10⁶and 28 ± 3 x 10⁶ respectively). In the FSP group, 30women were given a total of 52 treatment cycles; 14 clinicalpregnancies occurred in this group, giving a pregnancy rateof 26.9% per cycle and 46.7% per woman. In the IUI group, 28women were given a total of 51 treatment cycles; five clinicalpregnancies occurred, giving a pregnancy rate of 9.8% per cycleand 17.9% per woman. The pregnancy rates per cycle and per womanin the FSP group were significantly higher than in the IUI group(P < 0.05, chi-square test). This study indicates that inthe treatment of couples with unexplained infertility, Fallopiantube sperm perfusion (FSP) is more successful than intra-uterineinsemination (IUI).     

Endocrinology: High ovarian response in Yoruba African women during ovulation induction for assisted conception

Fertile Yoruba women from western Nigeria have a much higherincidence of naturally conceived multizygotic twin and tripletpregnancies than Caucasians. The objective of the present studywas to determine whether there are differences between infertileYoruba and Caucasian women in terms of ovarian response in stimulatedcycles for assisted conception. A total of 11 Yoruba women werescheduled for 14 in-vitro fertilization (IVF) and one gameteintra-Fallopian transfer (GIFT) cycles from 1990 to 1992. TheCaucasian group consisted of 209 women scheduled for 213 IVFand 22 GIFT cycles during the same period. Buserelin, 500 µgsubcutaneously daily, was started in the mid-luteal phase toachieve pituitary desensitization. Ovarian stimulation was withvariable amounts of menopausal gonadotrophins. Human chorionicgonadotrophin (HCG) was given to trigger the ovulatory process.The Yoruba and Caucasian groups were similar in age and bodyweight, but significantly more Yorubas (45 versus 11% P <0.005) had ultrasound features of polycystic ovary syndrome(PCOS). The serum oestradiol concentration (3024 versus 2058pg/ml; P < 0.05) and number of follicles >14 mm in diameter(15.5 versus 9.5; P < 0.05) on the day of HCG were higherin the Yoruba group. The ovarian hyperstimulation syndrome (OHSS)was also more prevalent in the Yoruba group (20 versus 5% P< 0.05). No difference was found in clinical pregnancy orembryo implantation rates. These results show a higher tendencytoward exaggerated ovarian response in infertile Yoruba thanCaucasian women, associated with a higher prevalence of PCOS.The risk of developing symptomatic OHSS is higher in Yorubawomen.     

Pregnancy: Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight

Serum concentrations of human chorionic gonadotrophin (HCG),Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasmaprotein A (PAPP-A), progesterone and oestradiol were measuredat weekly intervals between the fifth (embryo transfer plus3 weeks) and 13th week of gestation during the first trimesterof pregnancies achieved following in-vitro fertilization (IVF)and embryo transfer in a group of women who delivered before(n = 8) or at term (n = 52). Those women who had a preterm deliveryhad significantly lower concentrations of PAPP-A (weeks 7–13;P = 0.0001–0.028) and SP-1 (weeks 6–8 and 10–12;P = 0.004–0.04). After correction of birth weight forsex and gestational age at delivery, preterm delivery was foundnot to be associated with growth retardation. However, comparisonof the circulating concentrations of the substances analysedin mothers who delivered babies of < 85% of the 50th centileof the normal range of birth weight for a given gestationalage and sex, with those who delivered babies of >85% revealedthat the concentrations of HCG (P = 0.012–0.04 on weeks6–9) and SP-1 (P = 0.003–0.03 on weeks 7, 9–13)were significantly lower in the former group. Weak, inconsistentassociations were found between the circulating concentrationsof HCG, SP-1 and PAPP-A and both corrected birth weight andgestational age at delivery. Thus, both the gestational ageat delivery and low birth weight may be related to impairedplacental development/function during the first trimester.     

Ovary and Ovulation: Contralateral selection of dominant follicle favours pre-embryo development

Ovulation was studied using vaginosonography in a total of 410natural cycles of 123 women undergoing infertility treatment[267 intrauterine insemination (IUI) cycles of 103 women and143 in-vitro fertilization (IVF) cycles of 50 women]. None ofthe women received ovarian stimulation. Each follicle was measureddaily from 14 mm in diameter until formation of corpus luteumor oocyte retrieval. Contralateral ovulation as compared withthe preceding cycle occurred in 57% of the 410 cycles. Contralateralovulations occurred in 72% of cycles with a follicular phase<13 days. In cycles with a follicular phase of >14 days,ovulations occurred at random. The length of follicular phasein contralateral ovulation cycles (15.2 ± 3.2 days) wassignificantly (P < 0.05) shorter than that of ipsilateralovulation cycles (15.8 ± 2.8). During the 57% contralateralovulations in 143 IVF cycles, the rates of oocyte retrieval(89%), fertilization (69%), cleavage (90%) and embryo transfer(56%) were significantly higher than those of ipsilateral ovulations(69, 51, 64 and 23% respectively). The pregnancy rate of contralateralovulations (9%) was also higher, though not significantly, thanthat of ipsilateral ovulations (3%), although the pregnancyrates per transfer were similar (16 and 14% respectively). Thetotal pregnancy rate of both IUI and IVF was higher in contralateralthan in ipsilateral ovulation cycles (8.1 and 4.0% respectively).The dominant follicles in contralateral ovulation cycles showedsignificantly higher oestradiol/androstenedlone ratio (P <0.025) and oestradlol/testosterone + androstenedione ratio (P< 0.025), and lower androstenedione (P < 0.05) than thoseof ipsilateral ovulation cycles. There was no significant differencein oestradiol, progesterone and testosterone. These resultsindicate that the dominant follicles in contralateral ovulationcycles are healthier than those of ipsilateral ones. Local intra-ovarianfactors, e.g. from the corpus luteum, may negatively affectthe health of the dominant follicle and the enclosed oocyte.Therefore contralateral selection of the dominant follicle inthe succeeding cycle may favour pre-embryo development. Thechance of conceiving during a natural cycle may be affectedby the site of ovulation in the preceding cycle.     

Triggering of ovulation in human menopausal gonadotrophin-stimulated cycles: comparison between intravenously administered gonadotrophin-releasing hormone (100 and 500 {micro}g), GnRH agonist (buserelin, 500 {micro}g) and human chorionic gonadotrophin (10 000 IU)

We studied the peri-ovulatory and luteal phases in 38 humanmenopausal gonadotrophin (HMG)-stimulated cycles, in which ovulationwas triggered with four different i.v. bolus ovulation triggers:100 µg gonadotrophin-releasing hormone (GnRH; group A,n = 9), 500 µg GnRH agonist (GnRHa; group B, n = 10),10 000IU human chorionic gonadotrophin (HCG; group C, n = 10)and 500 µg GnRH (group D, n = 9). Endogenous luteinizinghormone (LH) surges occurred in all cycles of groups A, B andD. The rise was slowest but highest in group B (P < 0.0001)and lowest in group A. Although the t₀ serum oestradiol valueswere similar in all groups, day +8 oestradiol and day +4 and+8 progesterone concentrations were higher in group C (P <0.05). At day +4 and +8, serum LH concentrations were lowest(P < 0.01) but follicle stimulating hormone (FSH) concentrationswere higher. Clinically, day +8 luteal scores showed a moreconspicuous degree of ovarian hyperstimulation in the HCG group(P = 0.0292). Luteal insufficiency, defined as cycles with progesteroneconcentrations of <8 ng/ml, occurred much more frequentlyin groups A, B and D than in group C (day +4: P < 0.0003;day +8: P < 0.0001), despite progesterone supplementation.Three pregnancies (one in group C and two in group D) and onemoderate case of ovarian hyperstimulation syndrome (OHSS) (ina non-conceptional group D cycle) occurred. These findings showthat (i) ovulation occurs and pregnancy can be achieved followingan endogenous LH surge induced by GnRH and its agonists, (ii)a high frequency of luteal insufficiency occurs in such cycleseven with luteal supplementation and (iii) OHSS cannot be totallyprevented by this approach, although cycles with an endogenousLH surge in general result in fewer subclinical signs of ovarianhyperstimulation.     

Endocrinology: Growth hormone, oestradiol, progesterone and testosterone concentrations in follicular fluid after ovarian stimulation with various regimes for assisted reproduction

Follicular fluid samples and oocytes were obtained from 75 women(87 cycles), who participated in an assisted conception programme.Determinations of the concentration of oestradiol, progesterone,testosterone and growth hormone were performed in all follicularfluid samples. Patients were stimulated with the following regimes:group A (24 cycles, 94 samples), human menopausal gonadotrophin(HMG) (three ampoules/day) and human chorionic gonadotrophin(HCG); group B (23 cycles, 53 samples), HMG/HCG with prednisolone(7.5 mg/day) after cycle programming with oral contraceptives;group C (40 cycles, 60 samples), buserelin with HMG/HCG. Oestradiolconcentrations (mean ± SEM) were significantly higher(P < 0.05) in group A (320.1 ± 27.3 ng/ ml) and thoseof growth hormone in both groups A and C (3.8 ± 0.2 and3.2 ± 0.15 ng/ml, respectively), as compared to the othergroups, whereas progesterone and testosterone concentrationswere similar in all groups. The mean concentrations of oestradiol,progesterone, testosterone and growth hormone were significantlyhigher (P < 0.01) in follicular fluid with oocytes of intermediatematurity than with mature oocytes (382.5 ng/ml, 7847.5 ng/ml,1704.5 ng/dl and 3.7 ng/ml versus 217.8 ng/ml, 5488.4 ng/ml,1313.6 ng/dl and 2.7 ng/ml, respectively). On the other hand,only oestradiol concentrations were significantly higher infollicular fluid of fertilized compared to non-fertilized oocytes.Concentrations of the other hormones analysed, except growthhormone, were similar in follicular fluid from pregnant andnon-pregnant women after assisted reproduction. Growth hormone,on the other hand, was significantly lower (P < 0.05) infollicular fluid from pregnant compared to non-pregnant women(2.8 versus 3.5 ng/ml). It is concluded that intermediate maturityoocytes and oocytes which will be subsequently fertilized arefound in follicles with higher follicular fluid concentrationsof growth hormone and steroids. Moreover, oocytes leading topregnancy after in-vitro fertilization and embryo transfer arederived from follicles with lower growth hormone concentrationsin follicular fluid.     

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries

The elevated luteinizing hormone (LH) and androgen concentrationscharacteristic of women with polycystic ovaries (PCO) are consideredcrucial factors in their infertility. The somatostatin analogueoctreotide lowers LH and androgen concentrations in women withPCO. The effects of octreotide given concurrently with humanmenopausal gonadotrophin (HMG) were therefore compared withthat of HMG alone in 28 infertile women with PCO resistant toclomiphene. In 56 cycles of combined HMG and octreotide therapythere was more orderly follicular growth compared with the multiplefollicular development observed in 29 cycles in which HMG wasgiven alone (mean number of follicles > 15 mm diameter onthe day of human chorionic gonadotrophin (HCG) administration:2.5 ± 0.2 and 3.6 ± 0.4 respectively; P = 0.026).There was a significantly reduced number of cycles abandoned(>4 follicles > 15 mm diameter on day of HCG) in patientstreated with octreotide + HMG, so that HCG had to be withheldin only 5.4% of cycles compared to 24.1% with HMG alone (P <0.05). The incidence of hyperstimulation was also lower on combinedtreatment. Octreotide therapy resulted in a more ‘appropriate’hormonal milieu at the time of HCG injection, with lower LH,oestradiol, androstenedione and insulin concentrations. Althoughgrowth hormone concentration was similar on both regimens, significantlyhigher insulin growth factor-I concentrations were observedon the day of HCG in women on combined therapy than on HMG alone.     

Relationship of biochemical pregnancy to pre-ovulatory endometrial thickness and pattern in patients undergoing ovulation induction

In order to assess the relationship between pre-ovulatory endometrialthickness and pattern and biochemical pregnancy, the pregnancyoutcome was retrospectively analysed in 81 patients undergoingovulation induction evaluated by vaginal ultrasound on the dayof human chorionic gonadotrophin (HCG) administration or luteinizinghormone (LH) surge. Biochemical pregnancies occurred in 7/32(21.9%) pregnancies when endometrial thickness was <9 mm,compared to 0/49 when endometrial thickness was 9 mm on theday of HCG administration or LH surge (P < 0.0025). Clinicalabortions occurred in 5/32 (15.6%) pregnancies when endometrialthickness was 6–8 mm, compared to 6/49 (12.2%) when endometrialthickness was 6–8 mm (NS). Endometrial thickness was relatedto the cycle day of HCG or LH surge (r = 0.37, P < 0.001)but was unrelated to oestradiol level on the day of HCG administrationor LH surge (r = 0.12). Biochemical pregnancies were relatedto endometrial pattern (r = – 0.22, P = 0.02) but wereunrelated to maternal age or previous abortions. Clinical abortionswere related to age (r = 0.26, P = 0.01) and to previous abortion(r = 0.25, P = 0.013) but were unrelated to endometrial pattern.Neither biochemical pregnancy nor clinical abortion was relatedto oestradiol or LH levels on the day of HCG administrationor LH surge. These findings suggest that the majority of biochemicalpregnancies do not result from karyotypically abnormal embryos,as do clinical abortions.     

Pregnancy: Endometrial ultrasonography as a predictor of pregnancy in an in-vitro fertilization programme

The endometrial pattern and thickness were analysed by ultrasonographyin 139 cycles stimulated for in-vitro fertilization (IVF) onthe day of administration of human chorionic gonadotrophin (HCG).A semi-programmed schedule based on the pill + clomiphene citrate+ human menopausal gonadotrophin (HMG) was used in all cycles.On the day of HCG administration, endometrial pattern and thicknesswere assessed with an Ultramark 4 (ATL) ultrasound equippedwith a 5 MHz vaginal probe. Endometrial pattern I (a ‘tripleline’multilayer) was observed in a total of 105 cycles (76%), andpattern II (fully homogeneous and hyperechogenic in relationto myometrial tissue) in 34 (24%). The incidence of clinicalpregnancy did not differ (P = 0.52) between the groups withendometrial patterns I (23.8%) and II (29.4%). Endometrial thicknesson the day of HCG administration in the group with pattern I(8.4 ± 1.9 mm) was similar (P = 0.96) to that observedin the group with pattern II (8.4 ± 2.0 mm). In addition,the endometrial thickness of the patients who became pregnant(8.0 ± 1.7 mm) did not differ (P = 0.15) from that ofwomen who did not achieve pregnancy (8.6 ± 2.0 mm). Theconclusion from the present data is that ultrasonographic analysisof endometrial thickness and refringency on the day of HCG administrationhad no predictive value for conception in IVF cycles.     

Vaginal misoprostol enhances intrauterine insemination

This study examined whether the prostaglandin E(1) analogue misoprostol (400 microgram), when placed vaginally at the time of intrauterine insemination (IUI) improves pregnancy rates. A prospective, placebo-controlled, randomized and double-blind study involving 274 women in 494 IUI cycles resulted in a total of 64 pregnancies (13% per cycle). Misoprostol cycles totalled 253, with 43 pregnancies (17% per cycle), whereas placebo cycles totalled 241, with 21 pregnancies (9% per cycle). The cumulative pregnancy rate with misoprostol treatment was significantly greater than with placebo (P = 0.004, Cox proportional hazards regression). The benefit of misoprostol was seen in clomiphene cycles (14 versus 4%, P = 0.006), and was indicated in FSH cycles (33 versus 15%, borderline significance) and natural cycles (15.6 versus 7.7%, not significant), but was not seen in clomiphene/FSH cycles (18.2 versus 23.5%, not significant). Misoprostol treatment did not increase pain score on the day of IUI (1.1 versus 1.4) and at 1 day post IUI (0.6 versus 0.8). Complications were rare in both groups [six (2%) subject cycles in the misoprostol cycles compared with two (1%) in the placebo group]. It is concluded that the use of vaginal misoprostol may improve the chance for pregnancy in women having IUI in a wide variety of cycle types.     

Perifollicular vascularity as a potential variable affecting outcome in stimulated intrauterine insemination treatment cycles: a study using transvaginal power Doppler

BACKGROUND: The aim of the present study was to assess any potential relationship between perifollicular vascularity and outcome in an in-vivo environment following human chorionic gonadotrophin (HCG) administration. METHODS: A total of 182 unselected consecutive patients undergoing stimulated intrauterine insemination (IUI) cycles was recruited where the perifollicular vascularity of follicles > or =16 mm was studied using a subjective grading system and transvaginal power Doppler ultrasonography, 36 h after HCG administration. RESULTS: A total of 601 follicles was studied. The incidence of follicles showing high-grade perifollicular vascularity (3 and 4) was higher than those with low-grade vascularity (1 and 2) (80 versus 20%). Treatment cycles were divided according to uniformity of vascularity grades of follicles > or =16 mm on the day of IUI [55% all high (3/4) grade; 33% mixed (1/2 and 3/4) and 12% all low (1/2) grade]. The mean age and duration of subfertility were significantly higher (P < 0.05), whereas the number of follicles > or =16 mm pre/post HCG, serum oestradiol and incidence of ultrashort gonadotrophin-releasing hormone (GnRH) agonist use were all significantly lower (P < 0.05) in treatment cycles with uniformly low follicular vascularity grades compared with mixed or uniformly high-grade cycles. However, on subjecting the data to multiple logistic regression analysis, the only independent variables that affected pregnancy rates appeared to be serum oestradiol (OR 1.28, 1.01--1.62) and high-grade follicular vascularity (OR 2.41, 1.08--5.40). CONCLUSION: These data would suggest that perifollicular vascularity has an important role to play in the outcome of IUI cycles, and that power Doppler has the potential to refine the management of assisted reproduction treatment cycles.     

Intra-uterine insemination versus cyclic, low-dose prednisolone in couples with male antisperm antibodies

A total of 46 couples with male immunological infertility enteredthe trial at the infertility clinic of the Family Federationof Finland. The men all showed a positive mixed antiglobulinreaction to immunoglobulin G in their semen; 31 men were alsotested for sperm-bound IgA immunoglobulins by flow cytometry.Serum antisperm antibodies were checked in a tray agglutinationtest. The women showed normal reproductive endocrinology andat least one patent Fallopian tube. The couples were randomizedto undergo either up to three intra-uterine inseminations (IUI),or timed intercourse with cyclic, low-dose (20 mg) prednisolonetherapy of the men. Cross-over was carried out if no pregnancyoccurred in the first stage. Timing of ovulation was based onurinary luteinizing hormone assay and transvaginal ultrasonographicmeasurements. In all, 40 couples either completed the studyor the female partner conceived. IUI was significantly better(P = 0.04) with nine pregnancies than timed intercourse withprednisolone (one pregnancy). There were no significant associationsbetween antibody levels, sperm count or motility versus theincidence of pregnancy. In male immunological infertility, well-timedIUI is an effective treatment method: results are obtained rapidlyand steroidal side-effects can be avoided.     

Endocrinology: A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility

The use of gonadotrophin-releasing hormone agonist (GnRHa) incombination with human menopausal gonadotrophin (HMG) for ovulationinduction has been advocated for the treatment, particularlyby in-vitro fertilization (IVF) of various types of infertility.The present study was designed to compare the clinical efficacyof HMG alone with a short protocol of GnRHa/HMG for treatmentof unexplained infertility. A total of 91 couples with unexplainedinfertility were randomly assigned to one of two treatments;either HMG with intra-uterine insemination (IUI) (45 patients,62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments.Progesterone concentrations on the day of human chorionic gonadotrophin(HCG) administration were significantly higher in HMG (1.5 ±0.9 ng/ml) versus GnRHa/HMG (0.8 ± 0.6 ng/ml; P <0.05)cycles. Furthermore, GnRHa suppressed the occurrences ofpremature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively).However, there were no significant differences in HMG dose requirements,plasma oestradiol concentrations or follicular development onthe day of HCG administration between the two groups. Nor wereany significant differences found in the pregnancy rates betweenthe two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively).Our results suggest no beneficial effect of GnRHa/HMG comparedto HMG alone for the treatment of unexplained infertility, basedon pregnancy rates.     

Infertility: Higher pregnancy rates with a simple method for Fallopian tube sperm perfusion, using the cervical clamp double nut bivalve speculum in the treatment of unexplained infertility: a prospective randomized study

The object of this study was to evaluate the efficacy of thenewly developed cervical clamp double nut bivalve (DNB) speculumused for Fallopian tube sperm perfusion (FSP) with 4 ml of theinseminate, in comparison with standard intrauterine insemination(IUI) using a volume of 0.5 ml of the inseminate. Couples withunexplained infertility (n = 104), undergoing 202 cycles, wereenrolled in this study. Cycles were assigned randomly to eitherIUI (group A, n = 92) or FSP + DNB speculum^® (group B, n= 110). Ovarian stimulation was achieved using three differentovarian stimulation protocols in both groups. The age and folliculardevelopment of the patients were similar in both groups. Theserum hormonal measurements and the endometrial thickness wasalso similar on the day of human chorionic gonadotrophin (HCG)administration. The mean (± SD) number of motile spermatozoainseminated was 44.83 ± 16.57 x 10⁶ in group A and 42.68± 13.44 x 10⁶ in group B. In group A (IUI), 11 clinicalpregnancies (presence of gestational sac with heart beats) occurred(11.95% per cycle). In group B (FSP + DNB speculum^®) 29clinical pregnancies occurred (26.36% per cycle). These differenceswere statistically significant (P <0.001). The results ofthis study for the treatment of unexplained infertility indicatethat this simple, well tolerated, inexpensive method of usingthe DNB speculum for FSP is more successful than standard IUI.     

Placental and ovarian hormones in anembryonic pregnancy

The circulating levels of human chorionic gonadotrophin (HCG),pregnancy-associated plasma protein-A (PAPP-A), Schwangerschaftprotein 1 (SP-1), oestradiol and progesterone were measuredin 81 pregnant patients between 4 and 11 weeks gestation, followingin-vitro fertilization and embryo transfer. The patients weredivided as follows: singleton anembryonic pregnancies, n = 22;singleton pregnancies which spontaneously aborted followingthe demonstration of fetal heart activity, n = 7; and normalsingleton pregnancies, n = 52. The levels of all substancesmeasured were significantly reduced in women with anembryoniccompared to those with singleton pregnancies which proceededto term. The serum levels of SP-1, weeks 6–8 (P < 0.01);HCG, weeks 6–8 (P < 0.05); oestradiol, weeks 5–8(P < 0.05) and progesterone, weeks 6–8 (P < 0.05),were lower in anembryonic pregnancies than in those of pregnancieswhich spontaneously aborted. These differences may be a reflectionof the fact that miscarriage, after the demonstration of fetalheart activity, represents fetal demise at a later stage inpregnancy. In anembryonic pregnancies, significant associationswere found between HCG and both oestradiol and progesteronelevels from weeks 6 and 8, suggesting that in the absence ofan embryo, HCG is the prime determinant of steroid synthesisby the corpus luteum.     

Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH

BACKGROUND: The study was conducted to compare the results of intrauterine donor insemination (DI) under ovarian stimulation with either clomiphene citrate (CC), in a fixed protocol, or FSH, with ovarian monitoring. METHODS: Forty-nine patients were randomized using a computer-generated list to receive highly purified urinary FSH (starting dose of 150 IU) and were subjected to periodic vaginal ultrasound and estradiol determinations. HCG was given when > or =2 follicles (> or =17 mm) were identified and estradiol reached >400 pg/ml. Intrauterine insemination (IUI) was performed 36 h later. The other 51 received CC on a fixed protocol (100 mg/day from the day 5-10 of the ovarian cycle) with HCG being administered on the day 12, and IUI performed 36 h later. Up to six IUI cycles were performed on all patients if pregnancy was not reached before. Women failing to conceive in the CC group underwent IUI with FSH. The main outcome measures were intrauterine gestational sac observed by transvaginal ultrasound, per cycle and per woman pregnancy rate (PR) and multiple PR. RESULTS: The per cycle PR was significantly higher in the FSH group, 14.4% (30/209) versus 6.1% (16/261), as well as the per woman PR, 61.2% (30/49) versus 31.4% (16/51). 12.5% (2/16) of pregnancies obtained in the CC group were multiple, compared with 20% (6/30) in the FSH group. There were no triplets or higher order pregnancies in CC versus two in FSH (6.7% of pregnancies). Patients failing to conceive with CC, who later underwent intrauterine DI with FSH, had similar results to the primary FSH group: 54.3% PR per patient (19/35) and 16.0% per cycle (19/118), with a multiple PR of 31.6% (6/19). The PR for women starting with CC cycles and, if pregnancy was not obtained, continuing with six FSH cycles, was 69.2%. CONCLUSIONS: The PR obtained with CC stimulation was approximately half that obtained with FSH. There was a trend to lower multiple PR with CC. It is recommended that each case should be considered on an individual basis and the treatment options discussed with patients. In our opinion, CC could be a reasonable approach for young women with good prognosis, whereas in the remaining cases FSH would be the preferable method.     

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.     

The value of single versus repeated insemination in intra-uterine donor insemination cycles

Pregnancy rates per cycle of intra-uterine donor inseminationfollowing ovulation induction were compared retrospectivelyfor those patients having a single, and those having repeatedinsemination using frozen donor semen. Single insemination wasperformed in 69 cycles in which 15 women became pregnant (pregnancyrate = 22%). Of 65 cycles in which repeated insemination wasperformed, 16 women became pregnant (pregnancy rate = 25%).This difference in pregnancy rates was not statistically significant(x² = 3.6, P = 0.84). We conclude that cycle fecundity may notbe increased by repeating insemination.