Oocyte cryopreservation versus ovarian tissue cryopreservation for adult female oncofertility patients: a cost-effectiveness study.

PURPOSE: In December 2019, the American Society for Reproductive Medicine designated ovarian tissue cryopreservation (OTC) as no longer experimental and an alternative to oocyte cryopreservation (OC) for women receiving gonadotoxic therapy. Anticipating increased use of OTC, we compare the cost-effectiveness of OC versus OTC for fertility preservation in oncofertility patients. METHODS: A cost-effectiveness model to compare OC versus OTC was built from a payer perspective. Costs and probabilities were derived from the literature. The primary outcome for effectiveness was the percentage of patients who achieved live birth. Strategies were compared using incremental cost-effectiveness ratios (ICER). All inputs were varied widely in sensitivity analyses. RESULTS: In the base case, the estimated cost for OC was $16,588 and for OTC $10,032, with 1.56% achieving live birth after OC, and 1.0% after OTC. OC was more costly but more effective than OTC, with an ICER of $1,163,954 per live birth. In sensitivity analyses, OC was less expensive than OTC if utilization was greater than 63%, cost of OC prior to chemotherapy was less than $8100, cost of laparoscopy was greater than $13,700, or standardized discounted costs were used. CONCLUSIONS: With current published prices and utilization, OC is more costly but more effective than OTC. OC becomes cost-saving with increased utilization, when cost of OC prior to chemotherapy is markedly low, cost of laparoscopy is high, or standardized discounted oncofertility pricing is assumed. We identify the critical thresholds of OC and OTC that should be met to deliver more cost-effective care for oncofertility patients.

An objective volumetric method for assessment of ovarian follicular and luteal vascular flow using colour Doppler ultrasonography.

Our goal was to develop an objective computer-assisted volumetric method of assessing vascular flow from colour Doppler ultrasound data of ovarian structures recorded by free-hand movement. We hypothesized that a vascularity index (ratio of the region of blood flood to the region of ovarian structure) obtained from the three-dimensional volumetric analysis would be more precise (less variable) than conventional two-dimensional analysis of single images in estimating the functional status of the preovulatory follicles and corpus luteum. Doppler ultrasound cineloops of water buffaloes (Bubalus bubalis; n = 22) ovaries were recorded daily from 12 h before GnRH treatment to four days after ovulation. Cineloops were processed using Fiji and Imaris software packages for segmenting the area (two-dimensional analysis) and the volume (three-dimensional analysis) occupied by the blood-flow and associated tissue to calculate the vascularity index. For volumetric measurement, all images in a cineloop were used (i.e., no a-priori selection of images) while for two-dimensional analysis, three images from the region with apparent maximum vascularity were selected. The volumetric method was verified with theoretical ellipsoidal volume of the follicle (r = 0.96 P < 0.01) or corpus luteum (r = 0.58 P = 0.02). The variability in the follicular vascularity index among animals was lower using the volumetric method than two-dimensional analysis (0.018 ±â€¯0.002 vs 0.030 ±â€¯0.005, P < 0.01), while the variability for CL vascularity was similar between methods (P = 0.23). An increase in the follicular vascularity index was detected at 12 h after GnRH treatment using both methods (two-dimensional: 0.030 ±â€¯0.008, P < 0.01; three-dimensional: 0.016 ±â€¯0.006, P < 0.02). Buffaloes that ovulated tended to have a greater increase in 3D vascularity index than non-responding buffaloes (P = 0.06); the two-dimensional method was not able to detect these changes. Using the three-dimensional method, a moderate positive correlation (r = 0.59; P = 0.02) was evident between the follicular vascularity index at 14-16 h after GnRH treatment and follicular diameter. In conclusion, an objective volumetric method for assessing relative ovarian blood flow changes was developed using Doppler ultrasound cineloops recorded by free-hand movement. The 3-dimensional method eliminates the need for a-priori selection of images and is more precise as a result of decreased technical variability.

Highly sensitive assessment of neuroblastoma minimal residual disease in ovarian tissue using RT-qPCR-A strategy for improving the safety of fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation (OTC) is the only option available to preserve fertility in prepubertal females with neuroblastoma (NB), a childhood solid tumor that can spread to the ovaries, with a risk of reintroducing malignant cells after an ovarian graft. PROCEDURE: We set out to determine whether the analysis of TH (tyrosine hydroxylase), PHOX2B (paired-like homeobox 2b), and DCX (doublecortin) transcripts using quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) could be used to detect NB contamination in ovarian tissue. Analyses were performed on benign ovarian tissue from 20 healthy women between November 2014 and September 2015 at the University Hospital of Clermont-Ferrand. Pericystic benign ovarian tissues were collected and contaminated with increasing numbers of human NB cells (cell lines IMR-32 and SK-N-SH) before detection using RT-qPCR. RESULTS: TH and DCX transcripts were detected in uncontaminated ovarian tissue from all the donors, hampering the detection of small numbers of tumor cells. By contrast, PHOX2B was not detected in any uncontaminated ovarian fragment. PHOX2B levels were significantly increased from 10 NB cells. Our study is the first to evaluate minimal residual disease detection using NB mRNAs in human ovarian tissue. Only PHOX2B was a reliable marker of NB cells contaminating ovarian tissue. CONCLUSIONS: These results are encouraging and offer hope in the near future for grafting ovarian tissue in women who survive cancer, whose fertility has been jeopardized by treatment, and who could benefit from OTC without oncological risk.

Assessment of in vitro antiovulatory activities of nonsteroidal anti-inflammatory drugs and comparison with in vivo reproductive toxicities of medaka (Oryzias latipes).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used therapeutic agents; however, their pharmacological actions raise concerns about potential risks to the reproductive health of aquatic vertebrates. In the present study, a medaka ovulation assay was applied as an in vitro model to evaluate NSAID-induced antiovulatory activity. We first tested five NSAIDs, including diclofenac sodium (DCF), ketoprofen (KP), salicylic acid (SA), mefenamic acid (MA), and acetylsalicylic acid (ASA) for their antiovulatory activities toward the follicles isolated from the ovaries of spawning females. Of all the chemicals tested, DCF had the highest antiovulatory activity, with the concentration that caused 50% inhibition (IC50) (101 µM). MA was the second most potent inhibitor following DCF, but KP, SA, or ASA had little inhibitory effect on the ovulation of the follicles. The in vitro antiovulatory activity of five NSAIDs showed good correlation with data published on the inhibitory activity on human COX-2. Second, we selected DCF and SA as the most and least potent NSAIDs, respectively, and examined the effects on reproduction of intact fish in order to evaluate whether the ovulation assay was a reasonable predictor of potential reproductive effects in fish. Females exposed to DCF showed a concentration-dependent decrease in the number of spawned eggs and an increment in the gonadosomatic index (GSI), possibly due to an anovulation in the females. In contrast, neither fecundity nor the GSI of females decreased at up to 20 mg/L of SA, at which acute lethality to medaka was induced. In conclusion, the medaka ovulation assay reflected the potency of NSAID-induced antiovulatory activity and may thus serve as an in vitro model for the prediction of NSAID-induced reproductive toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1710-1719, 2016.

A Whole-Mount Approach for Accurate Quantitative and Spatial Assessment of Fetal Oocyte Dynamics in Mice.

Depletion of oocytes from the embryonic ovary is a key feature of mammalian oogenesis; however, the rational and molecular bases for this phenomenon remain poorly understood. Presently in the field, the most systematic analysis used to understand the effect of a given molecular pathway on fetal oocyte attrition is to count the number of oocytes in ovaries at different stages of development. This analysis is commonly done using a sampling method based on sectioning of the ovary, a technique that includes many laborious steps culminating in an inaccurate estimate of oocyte number contained within that ovary. This inability to generate data that are directly comparable between labs hinders the field and raises questions about the timing and rate of oocyte depletion. Therefore, we set out to implement a robust method that can be easily used by most research laboratories to study the dynamics of oogenesis during fetal mouse ovary development in both normal and experimental conditions. Here we describe an approach to accurately count the total number of oocytes in embryonic ovaries. This method is based on whole-mount immunofluorescence, tissue clearing with sucrose and ScaleA2 reagent, and automatic detection and counting of germ cells in intact ovaries using confocal microscopy and three-dimensional software analyses. We demonstrate the power of the method by assessing variation of fetal oocyte numbers between left and right ovaries and between litters of mice. Finally, we anticipate that the method could be adopted to the analysis of substages of meiotic prophase I and ovarian somatic cells.

Comparative assessment of the reproductive status of female Atlantic bluefin tuna from the Gulf of Mexico and the Mediterranean Sea.

Despite attention focused on the population status and rebuilding trajectory of Atlantic bluefin tuna (Thunnus thynnus), the reproduction and spawning biology remains poorly understood, especially in the NW Atlantic. At present, the eastern and western spawning populations are believed to exhibit different reproductive characteristics and, consequently, stock productivity. However, our study suggests that the two spawning populations, the Gulf of Mexico and the Mediterranean Sea, could show similar reproductive features and spawning strategies. Between 2007 and 2009, gonad samples from female Atlantic bluefin tuna were collected in the northern Gulf of Mexico (n = 147) and in the western Mediterranean Sea (n = 40). The histological and stereological analysis confirmed that sampled eastern and western bluefin tuna exhibit the same spawning duration (three months) but the spawning in the Gulf of Mexico begins one month earlier than in the Mediterranean Sea. Western bluefin tuna caught in the peak of the spawning season (May) showed a similar spawning frequency (60%) to the spawning peak observed in the Mediterranean Sea (June). Fecundity for the Gulf of Mexico fish (28.14 eggs · g(-1)) was lower but not significantly different than for fish sampled in the Mediterranean Sea (45.56 eggs · g(-1)). Our study represents the first comparative histological analysis of the eastern and western spawning stocks whose findings, combined with new determinations of size/age at maturity and possible alternative spawning areas, might suggest basic life history attributes warrant further scientific and management attention.

Co-registered pulse-echo/photoacoustic transvaginal probe for real time imaging of ovarian tissue.

We present the design and construction of a prototype imaging probe capable of co-registered pulse-echo ultrasound and photoacoustic (optoacoustic) imaging in real time. The probe consists of 36 fibers of 200 micron core diameter each that are distributed around a commercial transvaginal ultrasound transducer, and housed in a protective shield. Its performance was demonstrated by two sets of experiments. The first set involved imaging of blood flowing through a tube mimicking a blood vessel, the second set involved imaging of human ovaries ex vivo. The results suggest that the system along with the probe has great potential for imaging and characterizing of ovarian tissue in vivo.

Purification of oogonial stem cells from adult mouse and human ovaries: an assessment of the literature and a view toward the future.

Contemporary claims that mitotically active female germ line or oogonial stem cells (OSCs) exist and support oogenesis during postnatal life in mammals have been debated in the field of reproductive biology since March 2004, when a mouse study posed the first serious challenge to the dogma of a fixed pool of oocytes being endowed at birth in more than 50 years. Other studies have since been put forth that further question the validity of this dogma, including the isolation of OSCs from neonatal and adult mouse ovaries by 4 independent groups using multiple strategies. Two of these groups also reported that isolated mouse OSCs, once transplanted back into ovaries of adult female mice, differentiate into fully functional eggs that ovulate, fertilize, and produce healthy embryos and offspring. Arguably, one of the most significant advances in this emerging field was provided by a new research study published this year, which reported the successful isolation and functional characterization of OSCs from ovaries of reproductive age women. Two commentaries on this latest work, one cautiously supportive and one highly skeptical, were published soon afterward. This article evaluates the current literature regarding postnatal oogenesis in mammals and discusses important next steps for future work on OSC biology and function.

Ovaries on ice: freezing fertility in preadolescent female cancer patients.

As survival rates from childhood cancer increase, fertility preservation is becoming increasingly important. Alkylating agents and whole body irradiation, common treatments in childhood cancer, have detrimental effects on follicle viability in females. Currently, ovarian tissue cryopreservation (OTC) is the only option for fertility preservation available to preadolescent females. Ovarian tissue can be harvested for cryopreservation laparoscopically without delaying cancer treatment. Although OTC is an experimental and rapidly evolving area of research, it has shown success in humans, with several live births reported thus far. Therefore, an analysis of OTC and its suitability for preadolescent females is appropriate at this time. Future research directions will allow OTC to transition from an experimental method with limited availability to a viable option for preadolescent cancer patients. As research progresses, physicians must be aware of the current state of OTC, as well as ethical concerns, risks, and benefits of OTC as a fertility preserving option.

Fertility assessment in hybrids between monobrachially homologous Rb races of the house mouse from the island of Madeira: implications for modes of chromosomal evolution.

The speciation model of divergence by monobrachially homologous fusions (that is, with one arm in common) benefits from a wide conceptual acceptance, because heterozygotes between populations carrying such fusions suffer from high levels of meiotic dysfunction. The same meiotic configurations can also be generated by WART (whole-arm reciprocal translocation), rearrangements that are known to occur in mammals. Estimating the disadvantage of heterozygotes carrying monobrachially homologous fusions is required to evaluate the relevance of this mode of chromosomal evolution in diversification and speciation. House mice are an excellent study models because chromosomal races exist carrying monobrachially homologous fusions, and WARTs have been documented in this species. The fertility of heterozygote mice carrying the smallest number of monobrachially homologous fusions (that is, a chain of four chromosomes, C4) was investigated in laboratory-bred hybrids between two parapatric chromosomal races from the island of Madeira. Meiotic nondisjunction analyses and histological sections of testes showed that aneuploidy (16.7%) and germ cell death (50.9%) rates reached significantly higher mean values in hybrids than in homozygotes. In females, however, the histological analysis of ovarian follicle parameters revealed no significant differences between hybrid and homozygous individuals. Overall, the reproductive assays indicated that these C4-carrying hybrids were not sterile but showed an approximately 50% decrease in fertility compared to homozygous parental mice. Implications for modes of chromosomal evolution involving monobrachially homologous fusions are discussed.

Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophosphamide.

BACKGROUND: Reproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix) could promote ovarian protection against damage due to chemotherapy. METHODS: Forty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n=9) received placebo twice; group II (n=12) received placebo+cyclophosphamide (CPA); group III (n=12) received GnRHant+CPA; and group IV (n=9) received GnRHant+placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted. RESULTS: Cyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p<0.01). The offspring was markedly reduced by CPA treatment (group II, 3.00+/-1.33 pups vs. group I, 11.44+/-0.78 pups, p<0.01) and this effect was partly reversed by pre-treatment with GnRHant (group III, 7.00+/-1.31 pups). The ovarian cross-sectional area was not significantly different between groups, neither was the number of individual follicle types. However, rats in Group IV had a higher total number of ovarian follicles than those in the control group (17.1+/-1.22 vs. 10.9+/-0.70, p<0.05). CONCLUSION: The use of a GnRHant before CPA chemotherapy provided protection of fertility.

Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels.

BACKGROUND: Serum androgen levels correlate with ovarian sensitivity to follicle-stimulating hormone (FSH) but in practice, standard baseline serum testosterone (T) levels prior to in-vitro fertilization (IVF) may not be the most appropriate marker for determination. METHODS: Infertile women enrolled in an IVF programme were included in this study. Serum T and Delta4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH. RESULTS: The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone. CONCLUSIONS: Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

Cryopreservation and orthotopic transplantation of rat ovaries.

The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required.

Polymorphic social organization in an ant.

Identifying species exhibiting variation in social organization is an important step towards explaining the genetic and environmental factors underlying social evolution. In most studied populations of the ant Leptothorax acervorum, reproduction is shared among queens in multiple queen colonies (polygyny). By contrast, reports from other populations, but based on weaker evidence, suggest a single queen may monopolize all reproduction in multiple queen colonies (functional monogyny). Here we identify a marked polymorphism in social organization in this species, by conclusively showing that functional monogyny is exhibited in a Spanish population, showing that the social organization is stable and not purely a consequence of daughter queens overwintering, that daughter queen re-adoption is frequent and queen turnover is low. Importantly, we show that polygynous and functionally monogynous populations are not genetically distinct from one another based on mtDNA and nDNA. This suggests a recent evolutionary divergence between social phenotypes. Finally, when functionally monogynous and polygynous colonies were kept under identical laboratory conditions, social organization did not change, suggesting a genetic basis for the polymorphism. We discuss the implications of these findings to the study of reproductive skew.

[National guideline 'Cryopreservation of ovarian tissue']. / Richtlijn 'Cryopreservatie van ovariumweefsel'.

The treatment of children and young adults with cancer increasingly results in cure, but for a number of female patients this is at the expense of infertility. For women and girls with cancer and the wish to have children in the future, cryopreservation of ovarian tissue may be a solution in the absence of alternatives for the conservation of fertility. Because of the uncertain effectiveness and safety of cryopreservation of ovarian tissue, the Dutch national guideline 'Cryopreservation of ovarian tissue' advises removing and freezing ovarian tissue only if this is done within the framework of scientific research. Reimbursement of this procedure and financing of the relevant and necessary research have not yet been arranged.

Quantification and viability assessment of isolated bovine primordial and primary ovarian follicles retrieved through a standardized biopsy pick-up procedure.

The feasibility of repeated collection and enzymatic isolation of large numbers of viable primordial and primary follicles from living donor cows were tested. Ovarian cortical biopsies were collected transvaginally by the Biopsy Pick-Up (BPU) device, a modification of an Ovum Pick-Up instrument. Follicles were enzymatically isolated from the retrieved cortical tissue samples, and follicle viability was determined by a live/dead fluorescent assay. Six cows were subjected to BPU once per week during 4 consecutive weeks, and in each BPU session 4 cortical tissue samples were collected per ovary. Over the 4-week trial period, a total of 1443 primordial and primary follicles were collected, 1358 (94%) of which were primordial and 85 (6%) were primary follicles. In each BPU session, an average 60.1 +/- 10.7 (mean +/- SEM) primordial and primary follicles were isolated per cow. The number of follicles varied considerably throughout the trial period and between cows. Statistical analysis of the data, however, did not support the presence of any distinct trends in the follicle yields over time or between cows. A total of 111 enzymatically isolated follicles were analyzed for viability with fluorescent probes. The vast majority of isolated follicles (92.8%) were totally viable. We conclude that the standardized BPU procedure generates sufficiently large numbers of vital primordial and primary follicles, thus validating BPU as a new tool for research into early bovine follicular development.

Age-specific levels for basal follicle-stimulating hormone assessment of ovarian function.

OBJECTIVE: Traditionally, the most important measurement in the assessment of ovarian function has been age-independent baseline follicle-stimulating hormone (FSH) levels. The objective of this study was to characterize the continuum of ovarian function based on age-specific categories of baseline FSH. METHODS: In a cross-sectional historical cohort study we evaluated records of 434 patients with baseline FSH levels of less than 12 milli international units/mL that underwent ovulation induction for in vitro fertilization (IVF) with long gonadotropin-releasing hormone (GnRH) antagonist or GnRH agonist suppression and modal gonadotropin stimulation of 300 units of gonadotropins per day. In these patients with apparent normal ovarian function by current baseline FSH criteria and with routine ovarian stimulation, we assessed IVF cycle outcomes, including oocyte yields, based on age-specific baseline FSH levels, defined as levels less than or equal to the 95% confidence interval for each age group. RESULTS: Age-specific baseline FSH levels predicted the retrieval of fewer than or equal to four oocytes, with a positive predictive value of 19.5% and a negative predictive value of 88%. The Mantel-Haenszel common odds ratio for fewer than or equal to 4 oocyte production in the presence of premature ovarian aging was 2.8 (95% confidence interval 1.52-5.17; P<.001). CONCLUSION: These results suggest that, within generally accepted normal baseline FSH values, women with baseline FSH above the 95% confidence limits for age produce fewer oocytes in response to normal ovulation induction protocols compared with other women their age.

Assessment of fertility and reproductive toxicity in adult female mice after long-term exposure to Pueraria mirifica herb.

The present study investigated the effects of long-term administration of Pueraria mirifica (PM) at non-toxic doses on the ovarian function and fertility of adult female mice based on evaluation of hematological and biochemical parameters. Female mice were divided into 4 groups (36 mice/group). Groups 1-3 were orally treated with a dose of 0 (PM-0), 10 (PM-10) or 100 mg/kg BW/day PM (PM-100), and group 4 was subcutaneously injected with 200 mug/kg BW/day of synthetic estrogen diethylstilbestrol (DES). The treatment schedule was separated into treatment and post-treatment periods. The duration of each period was 8 weeks. The PM-10 mice exhibited regular estrous cycles, while the PM-100 and DES treatments induced prolonged estrous cycles. Although no changes were observed in the uterus and ovary weights of the mice after the PM-100 and DES treatments, hyperplasia of the uterine endothelium and a decrease in the number of growing ovarian follicles were detected. The changes in the ovarian histologies of the PM-100 and DES mice were related to reductions in the levels of LH and FSH, which subsequently caused a decrease in mating efficiency. Once the PM mice were able to copulate, they were capable of successfully becoming pregnant and mothering offspring. No abnormalities were observed in the external morphologies and reproductive organ weights of the 50-day-old offspring. In conclusion, our results suggest that long-term exposure to 100 mg/kg BW of PM has adverse effects on the mating efficiency and reproduction of adult female mice and that administration of 10 mg/kg BW of PM does not induce any changes in the hypothalamic-pituitary-ovarian-uterine axis.

Simple tools for assessment of ovarian reserve (OR): individual ovarian dimensions are reliable predictors of OR.

OBJECTIVE: To determine the association between individual ovarian dimensions, advancing age, and declining ovarian reserve (OR) in an infertile population. DESIGN: An ongoing prospective observational study. SETTING: Academic infertility practice. PATIENT(S): Sixty-nine premenopausal women presenting for the evaluation and management of infertility. INTERVENTION(S): Transvaginal ultrasound assessment of the ovarian dimensions (length, width, and overall diameter in cm) and evaluation of the OR status by measuring serum levels of FSH and E(2) in the early follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Relationship of the individual ovarian dimensions to age (years) and OR (reflected by historical maximal FSH levels). RESULT(S): A statistically significant decrease in three ovarian size parameters accompanied advancing age (ovarian width, r = -0.30; ovarian length, r = -0.24; and the mean overall ovarian diameter, r = -0.30). Levels of FSH demonstrated a significant and linear correlation with age (r = 0.39). Increasing levels of FSH (and hence declining OR) were associated with statistically significant declines in the mean ovarian width (r = -0.39), length (r = -0.38), and overall mean ovarian diameter (r = -.42), Patients with a known diagnosis of diminished OR demonstrated significantly reduced ovarian dimensions compared with patients with other infertility etiologies. Multivariate linear regression analysis confirmed individual ovarian measurements (width, length, and overall diameter) as independent predictors of OR (FSH levels) after adjusting for parameters that are known to influence ovarian size, i.e., age, smoking status, body mass index, and anovulation history. Ovarian width emerged as the strongest predictor of OR (largest beta coefficient and hence the strongest association with OR status), compared with ovarian length and the mean ovarian diameter. CONCLUSION(S): Single ovarian dimensions are reliable predictors of advancing age and declining OR status in premenopausal infertile women. The magnitude of this association is most robust for the ovarian width.

Avaliação pós-transplante de ovários íntegros e fatiados sem anastomose vascular / Endocrinological, morphological and gestational assessment of intact and sliced ovarian orthotopic reimplantation or transplantation without vascular pedicle

OBJETIVO: Avaliar a fertilização, bem como aspectos endócrinos e histológicos do ovário após seu reimplante ou transplante ortotópico, sem anastomose vascular. MÉTODOS: Foram utilizadas 56 coelhas da raça Nova Zelândia Branca e Califórnia distribuídas em: Grupo 1 (n=8) - controle, apenas laparotomia e laparorrafia; Grupo 2A (n=8) - reimplante ortotópico de ovários íntegros; Grupo 2B (n=8) - reimplante ortotópico de ovários fatiados; Grupo 2C (n=8) - reimplantes ovarianos de um lado, íntegros, e, do outro lado, fatiados; Grupo Grupo 3A (n=8) - transplante ortotópico de ovários íntegros; Grupo 3B (n=8) - transplante ortotópico de ovários fatiados; Grupo 3C (n=8) - transplantes ovarianos de um lado, íntegros, e, do outro lado, fatiados. A partir do terceiro mês pós-operatório, cada coelha foi colocada para cópula. Dosou-se o estradiol, a progesterona, o FSH e o LH no nono mês pós-operatório. Estudou as morfologias macro e microscópicas dos ovários, tubas e útero, de todas os animais. Os números de gestações e de filhotes foram avaliados por meio do teste Qui-quadrado e as dosagens hormonais foram comparadas pelo one-way Anova, seguido pelo teste de Tukey-Kramer. RESULTADOS: No Grupo 1, sete (87,5 por cento) coelhas engravidaram entre o segundo e terceiro meses após início da cópula. No Grupo 2, as gestações ocorreram entre o quinto e o oitavo meses pós-operatórios e, no Grupo 3, entre o quarto e o oitavo meses pós-operatórios. A porcentagem de gravidez observada foi de 37,5 por cento no Grupo 2A, 50 por cento no Grupo 2B e 2C, 37,5 por cento no Grupo 3A, 50 por cento no Grupo 3B e 62,5 por cento no Grupo 3C. Os níveis hormonais e o estudo morfofuncional dos ovários, tubas e úteros não apresentaram alterações. CONCLUSÃO: O reimplante ou transplante ovariano homógeno ortotópico sem pedículo vascular é eficaz para a manutenção de níveis normais de hormônios ovarianos e permitiu a fertilização natural.

OBJETIVE: To assess the natural pregnancy and to determine the morphofunctional aspects of ovaries of rabbits submitted to bilateral oophorectomy and orthotopic allogeneic or autologous intact and sliced ovarian transplantation without a vascular pedicle. METHODS: Fifty-six female New Zealand White and California rabbits were studied. The ovaries were removed and orthotopically transplanted or replaced without vascular anastomoses: Group 1 (n = 8), only laparotomy and laparorrhaphy were performed; Group 2A (n = 8) intact ovaries were reimplanted on both sides; Group 2B (n = 8) both ovaries were sliced and orthotopically reimplanted; Group 2C (n = 8), an intact ovary was reimplanted on one side and a sliced ovary on the other side; Group 3A (n = 8) intact ovaries were transplanted on both sides, Group 3B (n = 8) both ovaries were sliced and orthotopically transplanted, Group 3C (n = 8), an intact ovary was transplanted on one side and a sliced ovary on the other side. Three months later, the females were paired with males for copulation. Estradiol, progesterone, follicle stimulating hormone and luteinizing hormone levels were assessed. The morphological aspect of the ovaries was studied and the number of pregnancies and litters were also determined.Tthe number of successful pregnancies and the number of litters was compared between the groups by the chi-square test. One-way ANOVA and the Tukey-Kramer tests compared the hormonal dosages. The significance was of p < 0.05. RESULTS: Pregnancies occurred in seven (87.5 percent) rabbits of Group 1, in 37.5 percent in Groups 2A and 3A, in 50 percent of groups 2B, 2C and 3B, and in 62.5 percent of group 3C. Hormone levels and histology confirmed the vitality of all ovaries. CONCLUSION: Intact or sliced orthotopic allogeneic and autologous ovarian transplantation without a vascular pedicle is viable in rabbits, and preserves their fertility and hormonal functions.