Deciphering the oviductal extracellular vesicles content across the estrous cycle: implications for the gametes-oviduct interactions and the environment of the potential embryo.

BACKGROUND: The success of early reproductive events depends on an appropriate communication between gametes/embryos and the oviduct. Extracellular vesicles (EVs) contained in oviductal secretions have been suggested as new players in mediating this crucial cross-talk by transferring their cargo (proteins, mRNA and small ncRNA) from cell to cell. However, little is known about the oviductal EVs (oEVS) composition and their implications in the reproductive success. The aim of the study was to determine the oEVs content at protein, mRNA and small RNA level and to examine whether the oEVs content is under the hormonal influence of the estrous cycle. RESULTS: We identified the presence of oEVs, exosomes and microvesicles, in the bovine oviductal fluid at different stages of the estrous cycle (postovulatory-stage, early luteal phase, late luteal phase and pre-ovulatory stage) and demonstrated that their composition is under hormonal regulation. RNA-sequencing identified 903 differentially expressed transcripts (FDR < 0.001) in oEVs across the estrous cycle. Moreover, small RNA-Seq identified the presence of different types of ncRNAs (miRNAs, rRNA fragments, tRNA fragments, snRNA, snoRNA, and other ncRNAs), which were partially also under hormonal influence. Major differences were found between post-ovulatory and the rest of the stages analyzed for mRNAs. Interesting miRNAs identified in oEVs and showing differential abundance among stages, miR-34c and miR-449a, have been associated with defective cilia in the oviduct and infertility. Furthermore, functional annotation of the differentially abundant mRNAs identified functions related to exosome/vesicles, cilia expression, embryo development and many transcripts encoding ribosomal proteins. Moreover, the analysis of oEVs protein content also revealed changes across the estrous cycle. Mass spectrometry identified 336 clusters of proteins in oEVs, of which 170 were differentially abundant across the estrous cycle (p-value< 0.05, ratio < 0.5 or ratio > 2). Our data revealed proteins related to early embryo development and gamete-oviduct interactions as well as numerous ribosomal proteins. CONCLUSIONS: Our study provides with the first molecular signature of oEVs across the bovine estrous cycle, revealing marked differences between post- and pre-ovulatory stages. Our findings contribute to a better understanding of the potential role of oEVs as modulators of gamete/embryo-maternal interactions and their implications for the reproductive success.

From conception to birth - how endometriosis affects the development of each stage of reproductive life.

Increasing evidence suggests that female infertility is associated with endometriosis. Indeed, 40% of women with this disease are infertile. However, a causal relationship has not yet been established, and the possible pathophysiology of infertility in this disease also has not been completely elucidated. In this article, we analyze the mechanisms necessary to achieve a successful live birth in patients with this disease as well as the important steps of fertility, pregnancy and birth that can be impaired in these women. Specifically, we will review new advances in research on folliculogenesis, oocyte quality and sperm quality, egg fertilization, embryo quality, transport through fallopian tube and utero-tubal transport sperm, implantation defects, risk of miscarriage, risk during pregnancy and pre-term delivery. The physiopathology of these alterations and the clinical results of the studies are still very controversial. For these reasons, we can conclude that more research is needed to study the biological pathways of the fertility impairment caused by this disease.

Tumour necrosis factor-α is the signal induced by mating to shutdown a 2-methoxyestradiol nongenomic action necessary to accelerate oviductal egg transport in the rat.

Mating shut down a 2-methoxyestradiol (2ME) nongenomic action necessary to accelerate egg transport in the rat oviduct. Herein, we investigated whether tumour necrosis factor-α (TNF-α) participates in this mating effect. In unmated and mated rats, we determined the concentration of TNF-α in the oviductal fluid and the level of the mRNA for Tnf-a (Tnf) and their receptors Tnfrsf1a and Tnfrsf1b in the oviduct tissues. The distribution of the TNFRSF1A and TNFRSF1B proteins in the oviduct of unmated and mated was also assessed. Finally, we examined whether 2ME accelerates oviductal egg transport in unmated rats that were previously treated with a rat recombinant TNF-α alone or concomitant with a selective inhibitor of the NF-κB activity. Mating increased TNF-α in the oviductal fluid, but Tnf transcript was not detected in the oviduct. The mRNA for TNF-α receptors as well as their distribution was not affected by mating, although they were mainly localized in the endosalpinx. Administration of TNF-α into the oviduct of unmated rats prevented the effect of 2ME on egg transport. However, the NF-κB activity inhibitor did not revert this effect of TNF-α. These results indicate that mating increased TNF-α in the oviductal fluid, although this not associated with changes in the expression and localization of TNF-α receptors in the oviductal cells. Furthermore, TNF-α mimicked the effect of mating on the 2ME-induced egg transport acceleration, independently of the activation of NF-κB in the oviduct. We concluded that TNF-α is the signal induced by mating to shut down a 2ME nongenomic action in the rat oviduct.

[The structural basis for transport through the Fallopian tube]. / Struktúrny základ transportnej funkcie vajíckovodu.

The Fallopian tube has until recently been a neglected structure, bypassed by in vitro fertilization and seen only as a tube that transports the oocyte or early embryo to the uterus. More recently, its role is even more undervalued after the introduction of techniques of assisted reproduction, in which the Fallopian tubes become like unnecessary. The Fallopian tube performs several important functions. It captures the oocyte after ovulation, maintains and controls the migration of spermatozoa to the site of fertilization. It provides the special microenvironment for fertilization; nourishes the early embryo while it is being carried to the uterus and amplifies signals from embryo to the mother. In our article we conducted a systematic review of relevant articles found in PubMed, Scopus and ISI Web of Knowledge, focused on the new insights into the functional morphology of Fallopian tube. We described the possible function of muscle layer motility, ciliary activity and tubal fluid movement on transport of gamets / embryo, as well as we mentioned the negative factors (such as smoking, chlamydial infection or endometriosis) affecting the transport through the Fallopian tube.

Two consecutive intrauterine pregnancies following transperitoneal ovum migration.

CONTEXT: Transperitoneal migration is a mechanism for oocyte retrieval that is generally demonstrated in certain cases of ectopic pregnancy. However, the association between these two conditions is debatable. The rare occasions on which intrauterine pregnancy following transperitoneal migration can be documented are an opportunity for studying this topic. CASE REPORT: We report the case of a female with a history of salpingectomy due to an ectopic pregnancy at 31 years of age. Two subsequent pregnancies were intrauterine. In both of them, ultrasound revealed that the corpus luteum was located in the ovary ipsilateral to the salpingectomy. CONCLUSION: To our knowledge, this is the first reported case of two intrauterine pregnancies following transperitoneal migration, carried to term, and resulting in the delivery of two healthy children. The clinical and physiological implications are discussed.

Analysis of ciliary beat frequency and ovum transport ability in the mouse oviduct.

The oviduct is important in reproduction where fertilization occurs, and the fertilized eggs are conveyed to the uterus. Multi-ciliated cells of the oviductal epithelium and muscle contractions are believed to generate this unidirectional flow. Although there are many studies in human oviducts, there are few reports on mouse oviductal ciliary movements where we can dissect underlying genetic programs. To study ciliary movements in the mouse oviduct, we exposed the ovary-side of the oviduct (infundibulum) longitudinally and recorded the ciliary beatings in a hanging drop preparation. We calculated the ciliary beat frequency (CBF) by automated image analysis and found that the average CBF was 10.9 ± 3.3 and 8.5 ± 2.5 Hz (±standard deviation) during the diestrus and estrus stages, respectively. Mapping of the CBF to multiple locations in the epithelium showed that the cilia beat regularly at a local level, but have a range of frequencies within the entire plane. We also observed ova with cumulus cells were transported to the uterus side by the opened oviduct at the diestrus and estrus stages. These results suggest that the ciliated cells of the infundibulum can generate unidirectional flows and are able to deliver ova by their ciliary activities despite their discordance in beating periodicity.

Two consecutive intrauterine pregnancies following transperitoneal ovum migration / Duas gestações intrauterinas consecutivas após migração transperitoneal do óvulo

CONTEXT: Transperitoneal migration is a mechanism for oocyte retrieval that is generally demonstrated in certain cases of ectopic pregnancy. However, the association between these two conditions is debatable. The rare occasions on which intrauterine pregnancy following transperitoneal migration can be documented are an opportunity for studying this topic. CASE REPORT: We report the case of a female with a history of salpingectomy due to an ectopic pregnancy at 31 years of age. Two subsequent pregnancies were intrauterine. In both of them, ultrasound revealed that the corpus luteum was located in the ovary ipsilateral to the salpingectomy. CONCLUSION: To our knowledge, this is the first reported case of two intrauterine pregnancies following transperitoneal migration, carried to term, and resulting in the delivery of two healthy children. The clinical and physiological implications are discussed.

CONTEXTO: A migração transperitoneal é um mecanismo de captação do oócito demonstrado, em geral, em determinados casos de gravidez ectópica. No entanto, a associação entre ambas é discutível. As raras ocasiões em que uma gestação intrauterina após migração transperitoneal pode ser documentada são uma oportunidade para o estudo deste tópico. RELATO DE CASO: Relatamos o caso de uma mulher com salpingectomia aos 31 anos, por gravidez ectópica. Duas gestações subsequentes foram intrauterinas. Em ambas, ultrassonografia evidenciou presença do corpo lúteo em ovário do mesmo lado da salpingectomia. CONCLUSÃO: No nosso conhecimento, trata-se do primeiro caso relatado com duas gestações intrauterinas após migração transperitoneal, terminadas com o nascimento de duas crianças saudáveis. As implicações clínicas e fisiológicas são discutidas.

[Follicular fluid in mammals]. / Le liquide folliculaire chez les mammifères.

Follicular fluid is a complex extracellular fluid, semi-viscous and yellow in colour, which accumulates in the antrum of ovarian follicles during their growing phase. Follicular fluid provides the microenvironment within which the cumulus-oocyte complex matures and granulosa cells differentiate. Scientists agree that follicular fluid derives mainly from plasma via the vascular compartment in the follicle wall. However, it also contains factors produced locally by the follicle cells, the production of which varies during different reproductive states. The aim of this paper is to review current knowledge on the formation, composition and roles of follicular fluid.

New aspects of gamete transport, fertilization, and embryonic development in the oviduct gained by means of live cell imaging.

The integrity of gamete transport, fertilization, and early embryonic development in the oviduct are essential prerequisites for successful reproduction. Although the basic mechanisms of gamete transport, gamete interaction, and early embryogenesis are known in most mammals, the interactions between gametes and oviductal epithelium as well as the communication between the early embryo and the female reproductive tract remain to be elucidated. Recent techniques of live cell imaging such as digital videomicroscopy and confocal fluorescence microscopy are valuable tools that provide actual new insights into these interactions. By applying these techniques, the mechanisms of sperm transport, sperm storage, oocyte transport, gamete interaction, and early embryo-maternal crosstalk can be analyzed under in vivo or in situ conditions. Detailed knowledge of these very early and important processes creates the basis to develop new therapeutic concepts for subfertility and infertility and to improve the techniques of assisted reproduction. The current review will focus on a short description of recent techniques of live cell imaging in the reproductive tract followed by an overview of actual observations during the early events of reproduction.

Ciliary transport, gamete interaction, and effects of the early embryo in the oviduct: ex vivo analyses using a new digital videomicroscopic system in the cow.

Using a digital videomicroscopic analysis system in the bovine, we showed that the mechanisms of transport caused by ciliary beating are distinctly different in ampulla and isthmus of the oviduct. The average particle transport speed (PTS) in the oviduct (mean, 133 microm/sec) does not differ in the cycle (metestrus) and during pregnancy after implantation, but it is locally modulated at the site of the embryo. Using videomicroscopy, we were able to document that after entering the ampulla, the cumulus-oocyte complex (COC) is not transported by ciliary beating down the oviduct, but firmly attaches to the ampullar epithelium. This attachment is mediated by the cumulus cells. However, when a COC is degenerated, it is floating in the oviductal lumen. As soon as a vital COC is in the ampulla, the sperm bound in the sperm reservoir of the ampullar isthmic junction leave the reservoir and hurry to the oocyte. When a sperm has penetrated the zona pellucida, the COC detaches and continues its migration. Quantitative measurements showed that the early embryo is able to locally downregulate PTS during its migration down the oviduct. It locally changes the pattern of vascularization and induces the formation of secretory cells. Our studies imply that the oviductal epithelium is able to select vital oocytes. The early embryo is able to induce the formation of secretory cells, modify vascularization, and downregulate speed of transport, thus creating the prerequisite for the first embryo-maternal communication in the oviduct.

Absence of paternal accessory sex glands dysregulates preimplantation embryo cell cycle and causes early oviductal-uterine transit in the golden hamster in vivo.

We hypothesize that deletion of paternal accessory sex glands compromised developmental potential of preimplantation embryos because of dysregulation of blastomeric cell cycle regulators. Quantification by immunocytochemistry showed disrupted cyclicity of proliferating cell nuclear antigen, augmented p53 and p21 expression, and premature transit from oviduct to uterus.

Genital sensory stimulation shifts estradiol intraoviductal signaling from nongenomic to genomic pathways, independently from prolactin surges.

Estradiol (E2) accelerates oviductal egg transport through nongenomic pathways involving oviductal protein phosphorylation in non-mated rats, and through genomic pathways in mated rats. Here we investigated the ability of cervico-vaginal stimulation (CVS) to switch the mode of action of E2 in the absence of other male-associated components. Pro-estrous rats were subjected to CVS with a glass rod and 12 hours later were injected subcutaneously with E2 and intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg transport acceleration. This clearly indicates that CVS alone, without other mating-associated signals, is able to shift E2 signaling from nongenomic to genomic pathways. Since mating and CVS activate a neuroendocrine reflex that causes iterative prolactin (PRL) surges, the involvement of PRL pathway in this phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were not different on day 2 of the cycle (C2) or pregnancy (P2). Activated ST AT 5a/b (phosphorylated) was detected by Western blot on P2 in the ovary, but not in the oviduct, showing that mating does not stimulate this PRL signalling pathway in the oviduct. Other rats subjected to CVS in the evening of pro-estrus were treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did not block the E2-induced acceleration of egg transport suggesting that PRL surges are not essential to shift E2 signaling pathways in the oviduct. We conclude that CVS is one of the components of mating that shifts E2 signaling in the oviduct from nongenomic to genomic pathways, and this effect is independent of PRL surges elicited by mating.

Effect of oestradiol and progesterone on the instant and directional velocity of microsphere movements in the rat oviduct: gap junctions mediate the kinetic effect of oestradiol.

The oviducal transport of eggs to the uterus normally takes 72-96 h in the rat, but this is reduced to less than 20 h after a single injection of oestradiol (E2). This accelerated transport is associated with an increased frequency of pendular movements in the isthmic segment of the oviduct, with increased levels of the gap junction (GJ) component Connexin (Cx) 43, and is antagonised by progesterone (P). In the present study, we investigated the effect of these hormones on the instant and directional velocity of pendular movements and the role of the GJ and its Cx43 component in the kinetic response of the oviduct to E2 and P. Using microspheres as egg surrogates, microsphere instant velocity (MIV) was measured following treatment with E2, P or P + E2, which accelerate or delay egg transport. Microspheres were delivered into the oviduct of rats on Day 1 of pregnancy and their movement within the isthmic segment was recorded. Oestrogen increased MIV with faster movement towards the uterus. After P or P + E2, MIV was similar to that in the control group. Two GJ uncouplers, namely 18 alpha- and 18 beta-glycyrrhetinic acid, blocked the effect of E2 on MIV. Connexin 43 mRNA levels increased over that seen in control with all treatments. In conclusion, the effects of E2 on MIV resulted in faster movements that produced accelerated egg transport towards the uterus. Gap junctions are probably involved as smooth muscle synchronisers in this kinetic effect of E2, but the opposing effects of E2 and P are not exerted at the level of Cx43 transcription.

Endothelin-2 induces oviductal contraction via endothelin receptor subtype A in rats.

Proper function of the oviduct is critical to reproductive success with regulated contraction and relaxation facilitating transportation of the germ cells to the site of fertilization. Endothelin-2 (EDN2) is a potent vasoconstrictor produced by granulosa cells of the preovulatory follicle at the time of ovulation; however, whether this gonadotropin surge-induced peptide played a role in facilitating germ cell transportation by inducing oviductal contraction was unknown. The objectives of these experiments were (1) to determine whether the endothelin receptor system was present in the oviduct, (2) to test the hypothesis that EDN2 induces oviductal contraction via a specific endothelin receptor subtype, (3) to determine, as a possible alternate source of the ligand, whether mRNA for EDN2 was expressed in cumulus-oocyte complexes (COCs) within the oviduct, and (4) to determine whether EDN2 could overcome prostaglandin E(2) (PGE(2))-induced oviductal relaxation. Microarray and real-time PCR analysis indicated that mRNA for both the endothelin receptor subtypes (ET(A) and ET(B)) was present in the oviduct, whereas immunohistochemical examination revealed that ET(A) protein was the dominant isoform, present in the luminal epithelial cells of the oviduct. Real-time PCR analysis demonstrated that mRNA for EDN2 was expressed in COCs after ovulation. Isometric tension analysis indicated that EDN2 was a potent oviductal constrictor and that the contractile effect of EDN2 was mediated by the ET(A) and not the ET(B) receptor subtype. The oviductal contraction induced by EDN2 also reversed oviductal relaxation induced by PGE(2). In summary, ET(A) receptor-specific EDN2-induced contraction as a facilitator of oviductal function suggests a novel pathway involved in germ cell transport and hence mammalian fertility.

Induction of ovulation and natural oestrous cycling in the Stripe-faced Dunnart, Sminthopsis macroura.

Induced ovulation allows reproduction by otherwise infertile females, and is ideal for the captive breeding of endangered species where the population is aged or breeding is unsuccessful. A predictable time of ovulation after induction has not yet been achieved in polyovular marsupials. Ovulation was induced in Sminthopsis macroura using an initial injection of 20 IU equine serum gonadotrophin (eSG; Day 0), followed on Day 4 by either 20 IU eSG (n = 25) or 0.5 mg porcine luteinizing hormone (n = 26). I.p. hormone injection was given in the morning or early evening, and reproductive status was established prior to induction. Five non-cyclic animals began to cycle naturally following induction and one gave birth to a litter. The time of ovulation after the 1st injection (7.8 +/- 0.9 days) was significantly shorter (P = 0.000) and less variable than the previous study, mimicked the timing of natural cycling, and both natural and induced animals ovulated in the early morning. In vitro oocyte movement through the oviduct, observed for the first time in a marsupial, occurred in pulses. We estimated one group of oocytes could travel the length of the oviduct in 40 min, but it was probably around 4 h. The entire ovulation time (including multiple ovulations) was estimated at 7.5 h. This study has achieved a predictable timing of ovulation after stimulation, and induced noncyclic animals to cycle naturally and give birth, providing a modified methodology for use in captive breeding programs of endangered dasyurid marsupial species with low fecundity.

Genital Sensory Stimulation Shifts Estradiol Intraoviductal Signaling from Nongenomic to Genomic Pathways, Independently from Prolactin Surges

Estradiol (E2) accelerates oviductal egg transport through nongenomic pathways involving oviductal protein phosphorylation in non-mated rats, and through genomic pathways in mated rats. Here we investigated the ability of cervico-vaginal stimulation (CVS) to switch the mode of action of E2 in the absence of other male-associated components. Pro-estrous rats were subjected to CVS with a glass rod and 12 hours later were injected subcutaneously with E2 and intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg transport acceleration. This clearly indicates that CVS alone, without other mating-associated signals, is able to shift E2 signaling from nongenomic to genomic pathways. Since mating and CVS activate a neuroendocrine reflex that causes iterative prolactin (PRL) surges, the involvement of PRL pathway in this phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were not different on day 2 of the cycle (C2) or pregnancy (P2). Activated ST AT 5a/b (phosphorylated) was detected by Western blot on P2 in the ovary, but not in the oviduct, showing that mating does not stimulate this PRL signalling pathway in the oviduct. Other rats subjected to CVS in the evening of pro-estrus were treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did not block the E2-induced acceleration of egg transport suggesting that PRL surges are not essential to shift E2 signaling pathways in the oviduct. We conclude that CVS is one of the components of mating that shifts E2 signaling in the oviduct from nongenomic to genomic pathways, and this effect is independent of PRL surges elicited by mating.

Inositol triphosphate participates in an oestradiol nongenomic signalling pathway involved in accelerated oviductal transport in cycling rats.

Oestradiol (E(2)) accelerates oviductal transport of oocytes in cycling rats through a nongenomic pathway that involves the cAMP-PKA signalling cascade. Here we examined the role of the inositol triphosphate (IP3) and mitogen-activated protein kinase (MAPK) signalling cascades in this nongenomic pathway. Oestrous rats were injected with E(2) s.c. and intrabursally (i.b) with the selective inhibitors of phospholipase C (PLC) ET-18-OCH(3) or MAPK PD98059. The number of eggs in the oviduct assessed 24 h later showed that ET-18-OCH(3) blocked E(2)-induced egg transport acceleration, whereas PD98059 had no effect. Other oestrous rats were treated with E(2) s.c. and 1, 3 or 6 h later oviducts were excised and the levels of IP3 and phosphorylated MAPK p44/42 (activated) were determined by radioreceptor assay and western blot, respectively. Oestradiol administration increased IP3 level at 1 and 6 h after treatment, whereas activated MAPK p44/42 level was unchanged. Finally, we explored whether cAMP-PKA and PLC-IP3 signalling cascades are coupled. Inhibition of adenylyl cyclase by i.b. injection of SQ 22536 blocked the increase of IP3 levels induced by E(2), while inhibition of PLC by ET-18-OCH(3) had no effect on E(2)-induced PKA activity. Furthermore, activation of adenylyl cyclase by Forskolin increased oviductal IP3 levels. Thus, activation of PLC-IP3 by E(2) requires previous stimulation of cAMP-PKA. We conclude that the nongenomic pathway utilised by E(2) to accelerate oviductal transport of oocytes in cycling rats involves successive activation of the cAMP-PKA and PLC-IP3 signalling cascades and does not require activation of MAPK. These findings clearly illustrate a non-genomic pathway triggered by E(2) that regulates a complex physiologic process accomplished by an entire organ.

Diminished pregnancy rates in endometriosis due to impaired uterotubal transport assessed by hysterosalpingoscintigraphy.

OBJECTIVE: To investigate uterotubal transport by means of hysterosalpingoscintigraphy (HSSG) in women with and without endometriosis. DESIGN: A prospective observational study. SETTING: University Hospital, Department of Obstetrics and Gynaecology, Division of Reproductive Medicine and Gynaecologic Endocrinology with 350 in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles and 400 intrauterine insemination (IUI) cycles/year. POPULATION: Cases included 56 infertile women with laparoscopic proven endometriosis and patent fallopian tubes. Twenty-two women with partners suffering from male factor infertility served as controls. METHODS: A diagnostic cycle incorporating HSSG was performed. Subsequently, patients underwent either four cycles of timed intercourse (TI) or IUI in order to achieve pregnancy. If pregnancy did not occur, IVF or ICSI was performed. MAIN OUTCOME MEASURES: Evaluation of uterotubal transport capacity in women with endometriosis and healthy controls. RESULTS: Patients suffering from endometriosis (group I) showed a significant reduction in physiologic uterotubal transport function: While 20 patients (36%) had ipsi- or bilateral uterotubal transport, there was pathological uterotubal transport contralateral to the dominant follicle or a complete failure of transport capacity (negative HSSG) in 36 patients (64%). In the controls (group II), transport function was significantly different: 15 of 22 patients (68%) revealed ipsi- and bilateral tubal demonstration, while 5 patients (22%) showed contralateral transport and 2 patients (10%) showed negative HSSG (P= 0.01). Twenty-three pregnancies were observed (pregnancy rate: 29%). Eleven out of 14 (79%) women with ipsi- or bilateral tubal transport function fell pregnant by means of TI or IUI. In seven of nine patients (78%) with a failure in tubal transport, pregnancy was achieved by IVF/ICSI, despite acceptable semen parameters (P= 0.01). CONCLUSIONS: Endometriosis is significantly associated with a reduction in physiologic uterotubal transport capacity compared with controls. This resulted in diminished pregnancy rates even in women with normozoospermic partners. Therefore, IVF/ICSI may be required even when fallopian tubes are patent or semen quality is normal.

Cigarette smoke inhibits hamster oocyte pickup by increasing adhesion between the oocyte cumulus complex and oviductal cilia.

Previous research has shown that oocyte cumulus complex (OCC) pickup rate is inhibited in hamsters when oviducts and OCCs are simultaneously exposed to cigarette smoke solutions, independent of any effect on ciliary beat frequency. The purpose of this research was to determine whether smoke solutions caused a change in adhesion between the OCC and infundibulum of the oviduct and to determine whether a change in adhesion could account for decreased OCC pickup rate. OCC pickup rate and adhesion were measured before and after infundibula or OCCs recovered from acute in vitro exposures to mainstream and sidestream whole, gas, or particulate smoke solutions. Ciliary beat frequency was also measured on infundibula. Overall, smoke solutions decreased oocyte pickup rate 40% to 80% below control levels and increased adhesion 52% to 91% above control levels when infundibula were pretreated. A change in adhesion was observed in cases for which decreased OCC pickup rate could not be explained by a change in ciliary beat frequency. OCC pickup rate decreased 20% to 35% below control levels and adhesion increased 39% to 54% above control levels when OCCs were pretreated. These data show not only that cigarette smoke causes an increase in OCC adhesion to the oviduct, but also that there is a correlation between increased adhesion and decreased OCC pickup rate. The results also show that the both the OCC and oviduct are targets of cigarette smoke. The oviduct is more sensitive to the adverse effects of smoke; however, this may be caused by a combined impact on mechanisms involved in both adhesion and ciliary function.