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.     

Ovarian stimulation with buserelin/HMG/HCG: prospective randomized study of short versus long protocol

The combined administration of the gonadotrophin-releasing hormone(GnRH) agonist buserelin and human menopausal gonadotrophin(HMG) was evaluated in 527 cycles (428 patients) of an assistedreproduction programme. All women were randomly allocated accordingto the ovulation induction protocol into two groups: group I(short protocol; 318 cycles) was given buserelin (1 mg/day)intranasally from cycle day 1 and HMG (2 ampoules/day) fromday 3 until human chorionic gonadotrophin (HCG) administration:group H (long protocol; 209 cycles) was given buserelin (1 mg/day)intranasally from cycle day 1 for at least 14 days and then2 ampoules HMG/day were added, increasing progressively accordingto the ovarian response. The number (mean ± SEM) of folliclesdeveloped was higher in group II than in group I (9.1 ±0.4 versus 7.7 ± 0.3, respectively; P < 0.05). Moreoocytes were retrieved in group II (8.4 ± 0.5) than ingroup I (6.5 ± 0.3) (P < 0.001), as well as more embryos(6.3 ± 0.5 and 4.0 ± 0.3, respectively; P <0.001). Moreover, in group II there was a better correlationbetween oestradiol and the total follicular volume (r = 0.5391)on cycle day 0 compared with group I (r = 0.458), while oestradiolvalues were similar between the two groups. No differences wereobserved in the cancellation rate, fertilization rate and maturityof the oocytes between the two groups. The pregnancy rate pertransfer was slightly better in group II (25.8%) than in groupI (19.4%), but this difference was not significant. More stimulationdays were needed in group II than in group I (11.8 ±0.2 and 10 ± 0.2, respectively) (P < 0.001) and moreHMG ampoules (37.7 ± 1.4 and 27.9 ± 0.1, respectively)(P < 0.001). In conclusion, the administration of the longprotocol is associated with a higher number of follicles developed,oocytes retrieved and embryos obtained, while it seems morepromising concerning the pregnancy rates. Nevertheless, treatmentwith this protocol increases the stimulation days and the numberof HMG ampoules administered and hence the cost.     

Implantation: Endometrial thickness appears to be a significant factor in embryo implantation in in-vitro fertilization

To evaluate the role of endometrial thickness and pattern inin-vitro fertilization (IVF), these parameters were prospectivelymeasured in 516 cycles of IVF with embryo transfer at our clinic.Pregnancy and embryo implantation rates were assessed for eachmm of endometrial thickness and for each of three endometrialpatterns. Embryo implantation, clinical and ongoing pregnancyrates were significantly higher in the patients with an endometrialthickness >9 mm (24.4, 48.6 and 42.2% respectively) comparedwith those of <9 mm (14.3, 16.0 and 11.7% respectively; P< 0.005). Endometrial thickness was negatively influencedby age and positively influenced by oestradiol concentration.The majority of patients (69.8%) exhibited a ‘ring’endometrial pattern. Embryo implantation and clinical pregnancy(statistically significant), as well as ongoing pregnancy rates(not statistically significant), were lower in patients exhibitingthe ‘solid’ pattern. Endometrial thickness is independentof pattern in its effect on pregnancy outcome. In conclusion,endometrial thickness >9 mm as well as ring and intermediateendometrial patterns denoted a more favourable prognosis forpregnancy in IVF but thinner endometrium and those exhibitinga solid configuration had an acceptable pregnancy outcome.     

Endometrial pattern and thickness associated with pregnancy outcome after assisted reproduction technologies.

The endometrial pattern and thickness was analysed prospectively on the day of administration of human chorionic gonadotrophin (HCG) in 200 in-vitro fertilization (IVF), gamete intra-Fallopian transfer (GIFT) and tubal embryo transfer (TET) cycles. Increasing maturity of the endometrial pattern was positively correlated with oestradiol levels (r = 0.20; P = 0.005), number of mature eggs (r = 0.13; P less than 0.05) and the number of top quality embryos (r = 0.40; P less than 0.001). The endometrial thickness was positively correlated with the number of follicles greater than or equal to 15 mm (r = 0.15; P less than 0.02) and the cycle day on which HCG was administered (r = 0.14; P less than 0.03). It was unaffected by the dose of human menopausal gonadotrophin and was negatively correlated with the use of clomiphene citrate (r = 0.40; P less than 0.001). Fecundity was increased for IVF when the endometrial thickness was greater than or equal to 9 mm (P less than 0.05) and for GIFT and TET when a Type C triple-line endometrial pattern was present (P less than 0.05). Biochemical pregnancies for the combined methods increased from 2.5% of all pregnancies when the endometrial thickness was 9-13 mm, to 27.8% when the thickness was less than 9 mm or greater than 13 mm (P less than 0.01). Biochemical pregnancies occurred in 67% of IVF pregnancies when the endometrial thickness was greater than or equal to 3 mm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endometriosis: The relationship of endometriosis to endometrial sonographic studies prior to administration of human chorionic gonadotrophin in patients undergoing in-vitro fertilization and embryo transfer

The objective of this prospective comparative study was to investigatethe relationship of endometriosis to endometrial thickness andsonographic echo pattern prior to the administration of humanchorionic gonadotrophin (HCG). Patients were matched by ageand ovarian stimulation protocol. A total of 210 patients undergoingin-vitro fertilization (IVF) and embryo transfer at a university-relatedIVF centre were enlisted. Of these, 105 women with laparoscopicconfirmation of endometriosis were compared to an equal numberof patients with laparoscopic confirmation of no endometriosis.Mean endometrial thickness did not differ between the groups(12.7 ± 2.9 versus 12.2 ± 2.5 mm). The distributionof echo patterns was also the same, irrespective of diagnosis.Evaluation of clinical pregnancy rates showed no reduction inpatients with endometriosis, regardless of stage, nor when comparingpatients to controls. Endometriosis has no effect on the endometrialthickness or echo pattern measured by sonography prior to administrationof HCG or the pregnancy rates following IVF and embryo transfer.     

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.     

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.     

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.     

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.     

Adjuvant growth hormone therapy in poor responders to in-vitro fertilization: a prospective randomized placebo-controlled double-blind study

The objective of the study was to assess the effect of growthhormone (GH) supplementation to a combined gonado-trophin-releasinghormone agonist/human menopausal gonadotrophin (GnRHa/HMG) treatmentprotocol on ovarian response in ‘poor responders’undergoing in-vitro fertilization (IVF). GH or a placebo wereadministered in a prospective randomized double-blind manner.A total of 14 poor-responder patients (oestradiol < 500 pg/ml,less than three oocytes retrieved in two previous IVF cycles)were randomly allocated to a combined treatment of either GnRHa/HMG/GH (18 IU on alternate days, total dose 72 IU) or GnRHa/ HMGplacebo. No difference was found between the study and controlgroups in the number of HMG ampoules used, the number of follicles(>14 mm) and serum oestradiol concentrations on the day ofadministration of human chorionic gonadotrophin (HCG), the numberof oocytes retrieved and fertilized, and the number of embryostransferred. The GH group (n = 7) did not show a better ovulatoryresponse in the study cycles; mean ± SD serum oestradiolon day of HCG 411 ± 124 versus 493 ± 291 pg/ml,aspirated oocytes 2.2 ± 1.5 versus 1.9 ± 2.0.Interestingly, when the above results for the placebo groupwere compared with their previous cycles (serum oestradiol 403± 231 pg/ml; 0.4 ± 0.5 aspirated oocytes), a non-specificeffect was found. Follicular recruitment, oestradiol secretionby mature follicles and the number of oocytes retrieved in poorresponders were not improved by GH supplementation.     

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.     

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).     

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.     

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.     

Human prolactin release induced by follicle stimulating hormone, luteinizing hormone and human chorionic gonadotrophin

Plasma prolactin levels rise in stimulated cycles. To clarifythe effects of gonadotrophin on the lactotrophs, three studieswere performed. First, plasma concentrations of prolactin duringclomiphene citrate (CC)-human menopausal gonadotrophin (HMG)-humanchononic gonadotrophin (HCG) treatment of women enrolled forin-vitro fertilization (IYF) were compared with those duringHMG-HCG administration while under pituitary suppression witha gonadotrophin releasing hormone (GnRH) analogue (buserelin).Women suppressed with buserelin had higher basal levels of PRLin plasma (14.4 ± 4.3 nglml versus 6.9 ± 1.4 ng/ml,P<0.001). Only buserelin-suppressed women showed a significantrise in plasma prolactin before HCG administration, while bothpatient groups had marked prolactin peaks after HCG injection.This peak was higher in the buserelin group (71.9 ± 50.7ng/ml versus 52.6 ± 29.7 ng/ml). The second study showedthat plasma levels of prolactin of 6 post- menopausal womenwere significantly increased 48 h after an injection of 5000IU HCG, i.m. (24.9 ± 17.4 ng/ml versus 12.4 ±6.2 ng/ml P<0.05). Third, plasma prolactin was studied in5 women over 30 days after surgical castration. An upward trendwas observed similar to that of endogenous gonadotrophin, withthe change in prolactin values closely correlating with thechange in concentrations of follicule stimulating hormone (P<0.005).All these findings suggest that human gonadotrophins stimulatelactotrophs.     

Endocrinology: Daily measurements and in-vitro effects of human chorionic gonadotrophin in the early luteal phase

The purpose of the present study was to analyse daily measurementsof human chorionic gonadotrophin (HCG) in in-vitro fertilization(IVF) cycles and to reproduce the effects of HCG in vitro usinghuman granulosa—luteinized cells from the same patients.The study population consisted of nine women undergoing IVFbecause of tubal infertility in whom blood was drawn every 24h from the day of the ovulatory dose of HCG (10 000 IU) until6 days after ovum pick-up. Granulosa—luteal cells fromthe follicular aspirates were collected and cultured in vitroup to 6 days in the presence of increasing concentrations (0,0.01, 0.1, 1.0 and 100.0 IU/ml) of HCG. Serum progesterone andHCG in vivo as well as progesterone accumulation in vitro ondays 2, 4 and 6, were the main outcome measures. Maximum HCGconcentrations (0.25 IU/ml) were reached the day before ovumpick-up, and continuously decreased until day 6 after ovum retrieval.HCG did not stimulate progesterone production in vitro at anydose tested until day 6 after ovum pick-up. Then, 0.01 IU/mlresulted significantly (P < 0.05) stimulatory compared tocontrols, while 1.0 IU/ml was inhibitory (P < 0.05). It isconcluded that HCG supplementation in an IVF cycle is unnecessaryuntil day 6 after ovum pick-up. On day 6, progesterone productionis stimulated with very low concentrations of HCG.     

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.     

A double-blind cross-over controlled study to evaluate the effect of human biosynthetic growth hormone on ovarian stimulation in previous poor responders to in-vitro fertilization

The effect of exogenous human biosynthetic growth hormone (HGH;12 IU/day; Norditropin, Novo-Nordisk) on the response to ovarianstimulation using a buserelin/human menopausal gonadotrophin(HMG) regimen was assessed in women who had previously showna ‘poor response’ in spite of increasing doses ofHMG. Forty patients were recruited into a prospective double-blindplacebo-controlled study. The serum follicle stimulating hormone(FSH) on day 2–5 of a menstrual cycle (< 10 IU/I) wasused to exclude any peri-menopausal candidates. The urinary24 h GH secretion was normal in all patients. Thirty-three patientscompleted the study with 21 patients having human chorionicgonadotrophin (HCG) in both arms, thus providing a completeset of placebo control data. Of these 21 patients, the administrationof HGH compared to the placebo cycle resulted in increased serumconcentrations of fasting insulin on the 8th (median 3.9 versus5.8 mU/I; P < 0.0005) and13th (median 4.4 versus 5.8 mU/I;P < 0.05) day of HMG in those cycles receiving HGH. After8 days of co-treatment with HGH the number of cohort follicles(14–16.9 mm) was significantly increased, but this changewas not sustained on the day of HCG administration. No statisticaldifference in the serum oestradiol on the 8th day of HMG orday of HCG, length of the follicular phase, total dose of HMGused, or the number of oocytes collected was seen between theplacebo or HGH cycles. This study demonstrates that HGH doesnot improve the ovarian response to ovulation induction in previouspoor responders.     

Uterus and endometrium: Endometrial pattern in diethylstilboestrol-exposed women undergoing in-vitro fertilization may be the most significant predictor of pregnancy outcome

The objective of this study was to compare prospectively pregnancyoutcome as it is related to ultrasonic endometrial echo patternin women exposed to diethylstilboestrol (DES) in utero by theirmother's consumption with women not exposed to DES, all of whomwere undergoing in-vitro fertilization (TVF). Pregnancy outcomerelative to endometrial thickness and pattern was evaluatedin 540 cycles of IVF including DES (n = 50) and non-DES-exposed(n = 490) women. Endometrial patterns were designated as p1= solid; p2 = ring; and p3 = intermediate. DES patients exhibitedp1 more often than the majority of the non-DES-exposed group.There was no significant difference in endometrial thicknessamong the cycles where p1 was noted when comparing the DES (103mm) with the non-DES-exposed (10.7 mm) groups. Notably, withinthe group exhibiting p1, no pregnancies occurred in the 18 cyclesof DES-exposed women compared with a 39.2% clinical pregnancyand 36.5% delivery rate in the non-DES-exposed controls (P 0.0001 and P = 0.008 respectively). Pregnancy rates were notsignificantly different in the cycles where the other endometrialpatterns were found when comparing the two groups. The impactof uterine shape on pregnancy outcome was also investigated.A T-shaped uterine configuration was noted in 11 out of 18 (61.1%)cycles of DES-exposed women with pattern p1 compared with nineout of 23 (39.1%) with pattern p2. Of cycles where a T-shapeduterus was demonstrated, none out of 11 (0%) with pattern p1compared with four out of nine (44.4%) with pattern p2 resultedin pregnancy (P = 0.026). These data suggest that endometrialpattern is one of the most significant variables for pregnancyoutcome in DES-exposed women undergoing IVF.     

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.