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.     

Relationship of constructed follicular growth patterns in stimulated cycles to outcome after IVF

The growth patterns of 827 follicles have been constructed from ultrasound measurements made between day -7 and day -2 of the follicular phase (oocyte aspiration = day 0) as a part of the routine treatment of 107 in-vitro fertilization (IVF) patients. A distinctive pattern of growth which was characterized by rapid early growth and a later growth consistent with the 'conceptual pattern' of growth described by Zegers-Hochschild (1984) for natural cycles was shown to be highly correlated with a delivered pregnancy outcome. Every cycle where a delivered pregnancy resulted (n = 9) produced one or more follicles with this pattern of growth (11/69 follicles, 16%). In contrast, only 20% (20/98) of cycles with any other outcome (abnormal pregnancy, no pregnancy, no embryo formed) appeared to have a follicle conforming to this pattern (27/758 follicles, 3.6%). These observations suggest that the follicle growth pattern, with particular emphasis on the rate of early growth, may be a highly predictive indicator of the quality of follicle development and the subsequent pregnancy potential of the oocyte contained within.     

Expected contribution to serum oestradiol from individual ovarian follicles in unstimulated cycles

Data relating serum oestradiol concentration to follicle size in unstimulated cycles are lacking. We provide precise data on serum concentrations expected for any follicle diameter (FD) in the mid- to late follicular phase. Infertile women (n = 35) with apparently normal ovulatory cycles were studied in detail in 128 unstimulated monofollicular cycles leading to IVF. Using mathematical modelling to account for repeated cycles in the same woman, the relationship between serum oestradiol and FD was explored and reference ranges for serum oestradiol at individual FD were calculated. Serum oestradiol concentrations [number of patients, geometric mean, 95% confidence interval (CI)] at the onset of the LH surge were higher in 'fertilized' cycles (73, 1279, 1180-1378 pmol/l) compared with 'unfertilized' cycles (31, 1055, 929-1197 pmol/l, P: = 0.008) and 'no oocyte' cycles (24, 1064, 922-1227 pmol/l, P: = 0.03) respectively. In 'fertilized' cycles, oestradiol concentrations rose exponentially with FD and for each size of follicle the oestradiol distribution was skewed. Functional oocyte competence varied in apparently normal ovulatory cycles and was correlated with pre-ovulatory serum oestradiol but not FD. Serum oestradiol varies within wide limits for maturing follicles of any given diameter prior to the onset of the LH surge.     

Ovary and ovulation: Folliculocentesis: a novel research technique to investigate the intrafollicular endocrine microenvironment

During development of the dominant follicle, the avascular granulosacells and oocyte are exposed to the follicular fluid endocrinemicroenvironment. An alteration in the endocrine characteristicsof follicular fluid affects follicular steroidogenesis, oocytematuration, ovulation and subsequent corpus luteum function.In-vitro studies on pooled follicular fluid from ovarian specimenslacked temporal precision between menstrual and follicular endocrineevents. We have established a new technique, termed folliculocentesis(FC), to sample follicular fluid from the dominant ovarian folliclewithout compromising its growth or function during the mid-to late follicular phase. A total of 38 subjects with regularovulatory cycles each underwent two identical cycles of hormoneand follicle growth monitoring: one cycle served as the control,and FC was performed during the second cycle. During all cycles,plasma luteinizing hormone (LH), oestradiol and ultrasound monitoringof follicle growth were commenced on day 7 and continued untilafter ovulation. During FC cycles, 200 ul of follicular fluidwere aspirated from the dominant follicle using transvaginalultrasound guidance when the follicle diameter reached 10 mm.Six subjects were excluded from the study because of incompleteor invalid endocrine data. In all, 32 subjects completed boththe FC and control cycles. The follicle growth pattern, maximumfollicle diameter, plasma oestradiol, oestradiol peak, plasmaLH, LH surge and follicular phase length were similar duringFC and control cycles. A total of 50 valid follicular fluidsamples were obtained when the dominant follicle was sampledonce, twice or three times during the same cycle and from thesame follicle in 15, 16 and one subjects respectively. The follicularfluid samples contained steroid concentrations consistent withthose of the mid- to late follicular phase. We conclude thatthe FC procedure is safe, easy to perform and does not affectfollicle growth or hormone dynamics. Analysis of the follicularfluid samples is expected to provide us with valuable in-vivoinformation about ovarian endocrinology.     

Serum levels of free androstenedione, testosterone and oestradiol are lower in the follicular phase of conceptional than of non-conceptional cycles after ovarian stimulation with a gonadotrophin-releasing hormone agonist protocol.

Serum concentrations of total and free androstenedione, testosterone and oestradiol were followed during the follicular phase in women undergoing ovarian stimulation for treatment by in-vitro fertilization and embryo transfer (IVF-ET) and compared to those in natural unstimulated cycles. In addition, 10 conceptional and 18 non-conceptional cycles were compared in an attempt to understand the background for successful IVF cycles. The ultra-short gonadotrophin-releasing hormone agonist protocol was used for ovarian stimulation. Throughout the follicular phase, levels of total and free androstenedione and oestradiol were significantly lower in conceptional than in non-conceptional IVF cycles. In addition, levels of free testosterone during the follicular phase were significantly lower in women who conceived compared to non-conceptional IVF cycles, whereas levels of total testosterone were similar. Levels of both free and total androstenedione increased significantly from the second day of the menstrual cycle until oocyte retrieval in non-conceptional IVF cycles, whereas levels in conceptional IVF cycles and unstimulated cycles showed no increase. On the day of oocyte retrieval levels of free and total androstenedione were significantly higher in non-conceptional IVF cycles than in conceptional IVF cycles and unstimulated cycles, which were similar. This study suggests that appropriate levels of free biologically active androgens and oestradiol are important parameters for successful conception.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between human oocyte maturity, fertilization and follicular fluid growth factors

Follicular fluid concentrations of growth hormone (GH), insulin-likegrowth factor-I (IGF-I), epidermal growth factor (EGF) and oestradiolwere related to diversities in oocyte maturation and fertilizationamong oocytes obtained for invitro fertilization (IVF). Follicularfluid GH, IGF-I and oestradiol concentrations were significantlycorrelated with increasing follicular size. Follicles with immatureoocytes had concentrations of oestradiol that were significantlylower when compared to follicles with intermediate and matureoocytes. Follicular fluid EGF concentration was similar forall oocyte maturational stages. In follicular fluids with matureoocytes we found IGF-I and GH concentrations were significantlyhigher compared to those of follicular fluid with atretic oocytes.Follicular fluids with Immature and intermediate oocytes hadsimilar concentrations of GH and IGF-I to follicular fluid containingmature oocytes and higher concentrations than follicular fluidwith atretic oocytes. No statistically significant differencewas found between fertilized and unfertilized oocytes. We concludethat maturation of oocytes Is associated with higher concentrationsof GH, IGF-I and oestradiol, but follicular fluid IGF-I andGH concentrations cannot serve as a predictor for IVF.     

Complete and partial luteinized unruptured follicle syndrome after ovarian stimulation with clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin

A total of 31 clomiphene citrate/human menopausal gonadotrophin(HMG)/human chorionic gonadotrophin (HCG)-stimulated cyclesin 28 patients were investigated to determine the fate of eachof the matured follicles. A standard stimulation regimen wasadhered to, and ultrasound as well as hormonal monitoring wasperformed. All follicles were measured by vaginal ultrasoundat –12, +35 and +45 h relative to HCG administration andat 7 days after HCG administration. Of the 220 follicles, 107(48.6%) ruptured. The number of ruptured follicles per cyclewas correlated with the mid-luteal progesterone concentration(r = 0.63, P = 0.0005). The probability of follicular rupturewas related to follicular diameter at 12 h before HCG administration;6% of follicles <12 mm in diameter ruptured compared with87% of follicles 18–19 mm. A complete luteinized unrupturedfollicle (LUF) syndrome was observed in six cycles (20%). Inthese cycles, follicular growth and oestradiol, progesterone,luteinizing hormone (LH) and follicle stimulating hormone (FSH)concentrations at 12 h before HCG administration were similarto those in cycles with follicular rupture. However, mid-lutealprogesterone concentrations were lower in complete LUF cycles(46.97 ± 8.95 nmol/1 versus 108.74 ± 12.27 nmol/1;P = 0.02). These data demonstrate that in stimulated cyclesmany follicles, usually the smaller ones, fail to rupture, evenafter HCG administration. Complete LUF syndrome, despite a strongexogenous ovulatory signal, and the absence of any differencein peri-ovulatory hormonal parameters, indicates that the defectcausing LUF resides in the follicle itself and/or hormonal changesduring the follicular phase.     

Poor responders to ovulation induction: is proceeding to in-vitro fertilization worthwhile?

A 'poor response' in the context of in-vitro fertilization (IVF) can be defined as failure to produce an adequate number of mature follicles, and/or a peak oestradiol concentration less than a defined minimum. The cut-off points implied in this definition vary between different centres. Many opt to cancel the IVF cycle when their defined minimum concentrations are not reached despite the lack of evidence of improved outcome in subsequent cycles. Patients attending the Oxford Fertility Unit who are 'poor responders' have always been given the option of continuing with treatment. The first cycles of IVF in 124 patients, with normal day 3 follicle stimulating hormone (FSH), who produced less than five follicles within a 2 year period were studied. The patients were divided into three groups according to the number of follicles produced: A (one or two follicles; n = 33), B (three follicles; n = 33) and C (four follicles; n = 58). The three groups were similar in age, day 3 FSH, total gonadotrophin dose, duration of stimulation, peak oestradiol concentration, oocyte yield, fertilization rate and the clinical pregnancy rate. However, group A had a significantly higher oestradiol concentration per follicle (P < 0.001). The clinical pregnancy rate/cycle in the three groups was comparable to our overall rate in the study period (25.5%). This paper suggests that poor responders with a normal day 3 FSH may still achieve a pregnancy rate similar to that of normal responders.     

Endocrinology: Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation

The aim of the present study was to investigate whether reducingthe amount of luteinizing hormone (LH) in gonadotrophic preparationsimpairs follicular growth in in-vitro fertilization (IVF) cyclesduring suppression of endogenous LH levels. A selected groupof 20 IVF patients was randomly divided into two groups. Onegroup was treated with Org 31338 [follicle stimulating hormone(FSH)/LH 3: 1], the other group with Metrodin® (purifiedFSH), both during pituitary down-regulation with buserelin.A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrationsof FSH, LH, oestradiol and progesterone were determined frequentlyand serial ultrasound examinations were performed. Multiplefollicular growth with concomitant rise of oestradiol levelswas observed in all cycles. The duration of the stimulationphase was shorter in the group treated with Org 31338 than inthe group treated with Metrodin. The number of follicles andoocytes and the fertilization rate was larger and the mean embryoquality was higher in the Org 31338 group, but the differencesdid not reach statistical significance. No significant differenceswere found in hormonal values. In women with normal endocrineprofiles, lowering of the LH activity in gonadotrophic preparationsduring gonadotrophin-releasing hormone agonist treatment resultsin adequate ovarian stimulation. However, a preparation withsome LH needed a shorter stimulation than a purified FSH preparation.Whether the other beneficial effects of Org 31338 also occurin a larger population needs further investigation.     

Contribution of preovulatory-phase small follicles to the ovarian response in stimulated cycles.

The usual criteria for ovulation induction in stimulated cycles take into account the number of follicles greater than 14-16 mm in diameter. We have retrospectively investigated how the presence of small (8-12 mm) follicles at the time of the last scan influences the ovarian response for in-vitro fertilization (IVF). The mean number of small follicles was nearly constant (3.8 to 5.9) and did not correlate with the number of large (greater than 12 mm) follicles in various protocols for ovarian stimulation. In patients stimulated under the influence of a gonadotrophin releasing hormone (GnRH) agonist, the number of small follicles was correlated with the oestradiol (E2) peak level and with the number of recovered oocytes. Our data demonstrate a significant contribution of follicles less than or equal to 12 mm to peripheral E2 levels and oocyte production for IVF.     

Follicular vascularity is not predictive of pregnancy outcome in mild controlled ovarian stimulation and IUI cycles

BACKGROUND: Although follicular vascularity has been shown to be a good indicator of oocyte quality in IVF, scant evidence is currently available on the predictive value of this variable in terms of pregnancy rate during controlled ovarian stimulation (COS) and intrauterine insemination (IUI) cycles. METHODS: Three-hundred and eighteen patients who had received mild COS underwent transvaginal ultrasound scan before performing the IUI. Using power Doppler imaging, vascularity of follicles with a mean diameter > or =16 mm was graded into a three grades according to the circumference of the follicle in which flow was identified. When more than one follicle was observed, grading was performed for all of them, and the highest vascularity grade was recorded. RESULTS: Clinical pregnancy rate (number/total) in the low-, medium- and high-grade vascularity groups was 14.1% (14/99), 10.0% (10/100) and 11.8% (14/119), respectively (P = 0.66). Similar results were observed when only monofollicular cycles were considered. CONCLUSIONS: Follicular vascularity does not predict the chance of pregnancy in women undergoing mild COS and IUI cycles.     

Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth

We recently demonstrated, using transvaginal sonography, thatconception cycles in in-vitro fertilization (IVF) are associatedwith a significantly thicker endometrium at mid-cycle than non-conceptioncycles, suggesting that endometrial growth may influence implantation.In the present study, to examine whether the type of stimulationprotocol affects endometrial development, we compared the sonographicappearance of the endometrium in 22 patients randomized to receiveclomiphene citrate and human menopausal gonadotrophin (CC/HMG)and in 19 who received HMG alone. A significantly thicker endometriumwas observed in the HMG patients compared to the CC/HMG group(P < 0.005) throughout the follicular phase of the cycle,although serum concentrations of oestradiol (E₂) did not differin the two groups. Twenty-three patients (13 in the HMG groupand 10 in the CC/HMG group) had previous IVF cycles with CC/HMGstimulation in which endometrial thickness was measured. A thinendometrium recurred with subsequent CC/HMG cycles while increasedgrowth occurred with HMG only compared to previous CC/HMG cycles.Therefore, ultrasound examination of the endometrium in thisstudy demonstrated that CC results in a thinner endometriumthan HMG alone. We believe these findings may be of importancein improving pregnancy rates in IVF and possibly in other infertilitytherapy which involves the use of clomiphene citrate.     

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.     

Endocrinology: The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone

To evaluate the relative importance of follicle stimulatinghormone (FSH) and luteinizing hormone (LH) in follicular developmentand oocyte fertility in the human species, the use of recombinanthuman FSH, human menopausal gonadotrophin (HMG), and very highlypurified urinary human FSH (FSH-HP) plus oestradiol valeratefor ovarian stimulation and in-vitro fertilization (IVF) werecompared in three cycles in a woman with isolated congenitalgonadotrophin deficiency who had never been treated with ovarianstimulating agents. The total number of ampoules of gonadotrophinsused was lower in the HMG treatment cycle. Ovarian responseand IVF outcome in the three treatment cycles were as follows:(i) HMG cycle: normal follicular growth, normal pattern of oestradioland inhibin through the menstrual cycle, high fertilizationrate (93%); (ii) recombinant FSH cycle: normal follicular growth,low oestradiol and abnormal inhibin, finally poor rate of fertilization(28%); (iii) FSH-HP plus oestradiol valerate cycle: normal folliculargrowth, normal pattern of inhibin and poor fertilization rate(27%). Luteal plasma progesterone concentrations were much higherin the HMG treatment cycle. This case shows that FSH is theonly factor required in order to induce follicular growth inthe human, although LH or a product derived from its actionmay assist in order to achieve full follicular maturity andoocytes capable of fertilization. Though oestradiol might havea mediatory role in the process of follicular maturation, ourresults favour a direct primary role of LH in complete maturationof the follicle.     

Multiple pregnancy after in-vitro fertilization and embryo transfer: report of a quadruplet pregnancy and delivery

The first baby from in-vitro fertilization (IVF) was born in England in 1978 as a result of retrieval of a single preovulatory oocyte in the course of a natural cycle (Steptoe and Edwards, 1978). At present most programmes of IVF throughout the world do not use natural cycles producing only one oocyte, but rather multiple oocyte cycles produced by clomiphene citrate (CC), human menopausal gonadotrophin (HMG), or pure follicle stimulating hormone (FSH), either separately or in combination, sequentially or concomitantly, for the induction of multiple follicular maturation.     

Ovary and ovulation: Prediction of ovarian cycle outcome by follicular characteristics, stage 1

Both dominant and subdominant follicles have been identifiedand individually monitored over the follicular phases of 54natural cycles in 36 women. Population dynamics of all antralfollicles, visible by ultrasonography, in the ovary over theentire cycle have also been characterized for the first time.This has been accomplished by developing a new system of mappingand monitoring follicles, including a three-dimensional computerimaging model and correlation program. The different dominantfollicle types were characterized by their ultrasonographicproperties. Ovulatory follicles were rounded in shape and mid-rangeechogenic, with a smooth antral edge by late follicular phase.Luteinized unruptured follicles were round, had low echogenicityand a very smooth antral edge. Atretic follicles were irregularin shape and antral edge and had mid-range echogenicity. A furtherimportant finding was that follicle success appears to be relatedto timing of growth and to the subdominant follicle populationpresent in the ovary. An analysis of follicle population dynamicsin ovulatory cycles showed a drastic decrease in number at theend of the luteal phase, followed by a sharp increase at thebeginning of the follicular phase. This study has demonstratedthat characteristics of individual follicles and populationdynamics of both dominant and subdominant follicles are stronglyassociated with cycle outcome. These findings will contributetowards a predictive model of dominant follicle status and cycleoutcome. A new hypothesis of follicle competition has also beenproposed.     

Three-dimensional endometrial volume calculation and pregnancy rate in an in-vitro fertilization programme.

This study was designed to investigate the role of three-dimensional (3D) endometrial ultrasound in predicting the outcome of an in-vitro fertilization (IVF) programme. In 47 IVF cycles measurements of endometrial thickness and volume, as assessed by 3D transvaginal ultrasound on the day of oocyte retrieval, and concentrations of oestradiol and progesterone in the same patient sampled on the day of sonography, were related to the occurrence of a successful implantation. The overall pregnancy rate was 31.9% (15/47). Fifteen pregnant patients had a mean endometrial thickness and volume of 10. 8 +/- 2.3 mm (mean +/- SD) and 4.9 +/- 2.2 ml, respectively. Thirty-two non-pregnant patients had corresponding measurements of 11.8 +/- 3.4 mm and 5.8 +/- 3.4 ml respectively. Endometrial thickness varied widely in both groups, in pregnant patients from 6. 9 to 16.0 mm, in non-pregnant patients from 6.5 to 21.1 mm. Oestradiol concentrations were not significantly correlated with either endometrial thickness or volume. The conclusion from the present data is that 3D volume estimation of the endometrium as well as analysis of endometrial thickness on the day of oocyte retrieval had no predictive value for conception in IVF cycles.     

Primordial and pre-antral follicles are not commonly observed in IVF aspirates

BACKGROUND: Follicular fluid recovered from IVF patients has been proposed to be a valuable source of pre-antral and primary follicles for patient therapy and research. We evaluated the recovery of immature follicles in follicular fluid from 54 patients undergoing IVF using several techniques. METHODS: Fluid from each patient underwent several methods of follicle recovery including: filtration through a cell strainer, Ficoll-Paque density gradient, isolate density gradient, histological slide preparation, and enzymatic digestion with collagenase and DNase. RESULTS: 34 primordial and primary follicles, mean 0.63 +/- 0.27/patient, and 14 pre-antral follicles, mean 0.26 +/- 0.14/patient, were found in this study. The serum estradiol level on the day of HCG injection was significantly lower (P < 0.05) in patients in which immature follicles were recovered, compared with those without immature follicles in the follicular fluid (1779.9 +/- 167.6 versus 2246.6 +/- 153.2 pg/ml). There were no women with advanced maternal age (>39 years) who had immature follicles in the follicular fluid. CONCLUSIONS: Follicular fluid cannot be considered an efficient or reliable source of immature follicles. The presence of any immature follicles appears to be associated with cause of infertility, the random placement of the aspirating needle and may be related to the age of patient.     

Inhibin A, inhibin B and activin A in follicular fluid of infertile women with tubal damage, unexplained infertility and emdometriosis

PROBLEM: To measure and compare concentrations of inhibin A, inhibin B, activin A and oestradiol in the follicular fluid of women with endometriosis, tubal damage and unexplained infertility with oocyte quality and fertilising capacity. Also, to assess whether impaired follicular function in women with endometriosis might be related to altered inhibin or activin concentrations and whether this correlated. METHOD OF STUDY: Follicular fluids were collected from individual follicles during oocyte retrieval for in vitro fertilisation (IVF) in natural cycles. Inhibin A, inhibin B and activin A were measured using two-site enzyme immunoassay, and oestradiol was assayed by fluoro-immunometric method. RESULTS: Follicular fluid inhibin A levels were found to be significantly higher in women with endometriosis. Inhibin A was directly correlated with follicle size. There was no correlation between the levels of inhibin A, inhibin B, activin A and oocyte quality or fertilising capacity in the three groups of women. CONCLUSIONS: Follicular fluid concentration of inhibin A is elevated in follicles of women with endometriosis and is positively correlated with follicle maturation. However, we were unable to demonstrate any association between the follicular fluid concentrations of inhibin A, inhibin B, activin A or oestradiol and the quality and fertilisation capacity of oocytes in women with tubal damage, unexplained infertility or endometriosis.     

Anovulations in an ovary during two menstrual cycles enhance the pregnancy potential of oocytes matured in that ovary during the following third cycle

The aim of this study was to test whether ovulation from anovary affects the health of oocytes from dominant folliclesin that ovary two cycles later. A total of 80 women each withtwo intact ovaries underwent 270 treatment cycles (155 naturalcycles and 115 clomiphene citrate cycles) all showing unilateralovulation. The results from the in-vitro fertilization (IVF)treatment were grouped according to whether ovulation (O) oranovulation (A) (no ovulation) was observed in the ovary withdominant follicle during the treatment cycle in the previoustwo cycles: O-O, A-O, O-A and A-A (previous second cycle-previousfirst cycle). The rate of pre-embryo formation in A-A was significantlyhigher than that of O-A. The pregnancy rate in A-A (29%) wasalso higher than those of O-A (13%), A-O (9%) and O-O (5%).These rates increased from O-O to A-A as the number of previousovulations in an ovary decreased. The presence of a corpus luteumand/or a dominant follicle is likely to exert local negativeeffects on the health of the oocyte contained in the follicleselected to ovulate up to two cycles later. Anovulations inan ovary for two menstrual cycles may therefore provide improvedconditions for the development of a healthier oocyte with anincreased pregnancy potential.